Chapter 4. Biology and Diseases of Rats Flashcards

1
Q

What is the scientific classification of the rat?

A

Rattus norvegicus
Order Rodentia
Family Muridae
Genus Rattus - contains at least 56 species

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2
Q

Norway rat

A

Rattus norvegicus

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3
Q

What is the maxillary recess (sinus) in the rat?

A

Located between the maxillary bone and the lateral lamina of the ethmoid bone. Contains the lateral nasal gland (Steno’s gland)

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4
Q

Steno’s gland (lateral nasal gland)

A

Has morphologic similarities to a serous salivary gland. Secretes a watery product discharged at the rostral end of the nasal turbinate. This secretion may act to regulate the viscosity of the mucus layer overlying the nasal epithelium.

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5
Q

How many lung lobes does the rat have?

A

Five. Left lung is single lobed. Right lung has cranial, middle, accessory, and caudal lobes.

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6
Q

What is unique about the pulmonary vein in rats?

A

Contains cardiac striated muscle fibers within its wall that an contiguous with those in the heart.

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7
Q

How is bronchoconstriction controlled in the rat?

A

By vagal tone. The rat does not have an adrenergic nerve supply in the bronchial musculature.

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8
Q

What are the accessory sex glands in male rats?

A

Paired bulbourethral glands (Cowper’s glands) at the base of the penis - open into the dorsal surface of the urethral flexure.
Within the abdominal cavity and surrounding the bladder are large vesicular glands (seminal vesicles) and the prostate gland.

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9
Q

How many lobes does the prostate gland in a male rat have?

A

Three. Dorsocranial (coagulation gland), ventral, and dorsolateral.

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10
Q

What type of uterus do rats have?

A

Bicornate uterus, although the uterine horns appear fused distally there are two distinct ossa uteri and cervices.

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11
Q

Describe the kidneys of rats.

A

Unipapillate, like other rodents. The right kidney is more cranial than the left (cranial edge at L1 and caudal edge at level of L3)

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12
Q

Why is the rat a common model for investigating nephron transport?

A

Can investigate with an in vivo micropuncture system, because of the presence of superficial nephrons in the renal cortex.

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13
Q

Describe unique features of the rat brain.

A

Large olfactory bulbs, a lissencephalic (smooth) cerebrum, two parafloccular lobes of the cerebellum - lie in deep sockets of the periotic capsule of the skull.
The hypophysis (pituitary gland) lies beneath the optic chiasma and is attached to the base of the brain by a thn hollow stalk - the infundibulum.
Rats lack a foramen of Magendie (links fourth ventricle to cisterna magna in humans).

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14
Q

Where do the spinal cord and filum terminale in rats end?

A
Spinal cord ends at the fourth lumbar vetebra.
Filum terminale (extension of pia mate, functions to suspend cord in CSF) ends at the level of the tail beyond the third caudal nerves.
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15
Q

Where is the recommended site for cardiocentesis in rats?

A

Along left thoracic wall between third and fifth ribs - heart is exposed to the thoracic wall in this area.

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16
Q

Describe the blood supply to the atria in rats.

A

Unlike in higher mammals, the blood supply to the atria in rats is largely extracoronary from branches of the internal mammary and subclavian arteries.

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17
Q

Black rat

A

Rattus rattus
R. rattus preceded R. norvegicus in migration from Asia to Europe and the Americas by several hundred years.
R. rattus reached Europe in the 12th century, Americas in 16th century.
R. norvegicus emerged in the 18th century in Europe, 19th century in Western Hemisphere.

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18
Q

Why has the Norway rat largely displaced the the black rat globally?

A

Norway’s rat’s larger size and aggressiveness

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19
Q

What is the history of the albino R. norvegicus rat?

A

Domesticated and used in Europe and America in the 1800s as prey for a sport (rat baiting) where terrier dogs would hunt rats in a pit. Because of the large number of rats needed, wild rats were purpose-bred and albinos were selected out by hobbyists.

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20
Q

What were some of the early experimental uses of rats?

A

Nutritional research with fasting studies as far back as at least 1828.
Used by Savory in 1863 in protein studies.
J.M. Philipeaux reported on effects of adrenalectomy in albino rats in 1856.
Used only sporadically in Europe and North America for research until ~1890.

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21
Q

What was the Wistar Institute?

A

Henry H. Donaldson & Milton Greenman at the Wistar Institute in the early 20th Century were pivotal in the development of the rat for reasearch use. Did much to produce and define early stocks of lab rats.

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22
Q

List some of the research uses for rats.

A

A standard species for toxicological, teratological, and carcinogenesis testing by the pharmaceutical industry and governmental regulatory agencies.
Use in behavioral, neurological, nutritional, and endocrinology.

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23
Q

ACI

A

Inbred strain used for: congenital genitourinary anomalies, prostatic adenocarcinomas

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24
Q

BB/Wor

A

Inbred strain used for: Juvenile insulin-dependent diabetes mellitus

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25
Q

BN (Brown Norway)

A

Inbred strain used for: Inducible, transplantable, myeloid leukemia, hydronephrosis, bladder carcinoma

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26
Q

BUF (Buffalo)

A

Inbred strain used for: Spontaneous autoimmune thyroiditis, host for transplantable Morris hepatoma

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27
Q

COP (Copenhagen)

A

Inbred strain used for: Prostate adenocarcinoma

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28
Q

F-344 (Fischer 344)

A

Inbred rat model for National Toxicology Program’s Carcinogen Bioassay Program and the National Institute of Aging

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29
Q

LEW (Lewis)

A

Inbred strain used for: Multiple sclerosis, various experimentally induced autoimmune diseases

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30
Q

LOU/C

A

Inbred strain used for: Myeloma, production of IgG autoantibody

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31
Q

SHR (spontaneous hypertensive rat)

A

Inbred strain used for: Hypertension, cardiovascular research

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32
Q

WF (Wistar-Furth)

A

Inbred strain used for: Mononuclear cell leukemia

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33
Q

Zucker

A

Inbred strain used for: Obesity

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34
Q

Brattleboro

A

Mutant strain used for: Diabetes insipidus (autosomal recessive)

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35
Q

Gunn

A

Mutant strain used for: Jaundice, kernicterus (autosomal recessive)

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36
Q

Nude

A

Mutant strain used for: T cell deficient (autosomal recessive)

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37
Q

Obese SHR

A

Mutant strain used for: Type 4 hyperlipoproteinemia (autosomal recessive)

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38
Q

Recommended room temperature for rats

A

70-76 deg F

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39
Q

Recommended room humidity for rats.

A

30-70%

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40
Q

Recommended room air changes per hour for rats.

A

10-15 air changes/hour are sufficient to compensate for heat load and the generation of NH3 and CO2 from animals

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41
Q

Recommended light intensity at cage level for rats.

A

130-325 lux is recommended to prevent retinopathy.
Rats are particularly susceptible to phototoxic retinopathy.
Management precautions such as not having exposed cages on the top shelves of tall racks should also be considered.

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42
Q

Why should rats be housed on solid-bottomed floors?

A

Unless there is an experimental need, rats should be housed on solid-bottomed instead of wire-bottomed cages to help prevent pododermatitis and injuries that are frequently associated with wire floors.

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43
Q

What are the most frequently used materials for solid-bottom rat cages?

A

Polycarbonate and polypropylene.
Polycarbonate is often preferred because it may be autoclaved repeatedly without damage and because its translucency allows for observation of animals.
Sold bottom cages should typically be sanitized 1-2 times per week; a less frequent cycle may be appropriate if cage density is very low, there are perinatal considerations, or ventilated cages are used.

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44
Q

Describe the tail lengths of different rat species.

A

Norway rat = tail ~85% the length of the body.

Black rat = tail is distinctly longer than the body

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45
Q

What is the hair growth cycle in young rats?

A

Resting period = 17 days, growing period = 17 days, repeats.

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46
Q

How many teats do rats have?

A

Usually 12; 3 pectoral pairs & 3 abdominal pairs.

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47
Q

Rank smallest to largest: Sprague Dawley, Wistar, Fischer 344

A

Outbred Sprague Dawley bigger than outbred Wistar; and inbred Fischer 344 smaller than both outbreds

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48
Q

Describe anatomic features of the rat eye.

A

Eyes are exophthalmic = increased risk of injury from trauma or during anesthesia.
Eyelids well developed & only corneas are visible.
Cornea moistened by secretions from lacrimal and Harderian glands.
Harderian gland is located medially to the orbit.
Orbital venous plexus has slightly different anatomy than the orbital sinus in the mouse, but can still be used for blood collection.
Rats do NOT have robust color vision.

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49
Q

What is chromodacryorrhea?

A

Production of Harderian gland products containing porphyrin.
The porphyrins will fluoresce; it has been suggested that the Harderian gland may have a function as a modulator of light-mediated responses

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50
Q

Describe the color vision of rats.

A

Dichromatic color vision with two types of cones; one cone type response to UV light with response centered around 359nm. The longer wavelength cone and rod have peak sensitivity around 505-509nm. (Why dim red lighting around ~625nm is used; however even dim red light can affect their photoperiodic physiology.)

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51
Q

What is the vomeronasal organ?

A

The vomeronasal organ (VNO) - essential to normal rodent reproductive behavior

i. When male rodents engage in anogential investigation of females prior to mounting, vaginal chemosignals are maneuvered to the roof of the mouth, then “pumped” through the nasopalatine duct into the opening of the VNO.
ii. Other signals may enter via the external nares (nostrils) and may be pulled down to the VNO from the floor of the nares.
iii. Neural information moves from the VNO to the accessory olfactory bulbs via the vomeronasal nerve bundle; thus, information originally obtained from the activation of VNO receptors is processed by the accessory olfactory bulbs.
iv. Information from the olfactory receptors is processed separately in the main olfactory bulbs

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52
Q

What is the hearing range of rats?

A

250 Hz to nearly 80 kHz; most sensitive hearing is in range of 8-32 kHz.

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53
Q

What is the ultrasonic range of hearing and vocalization in rats?

A

22-80 kHz.
Important to minimize ultrasonic noise in animal facilities (some things known to cause ultrasonic noise: some types of occupancy sensors, some types of energy-efficient high-frequency electronic ballasts that are used to drive fluorescent lamps).

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54
Q

What are vibrissae?

A

Extremely important sensory organ for touch in rats - whiskers.

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55
Q

What bones make up the skull of the rat?

A

Paired nasal, premaxillary, maxillary, zygoma, palatine, lacrimal, frontal, parietal, squamosal, periotic capsule, tympanic bulla, and mandible; six auditory ossicles; four turbinates; single vomer, ethmoid, basisphenoid, presphenoid, occipital ,interparietal, and hyoid bones.

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56
Q

What is the vertebral column formula for rats?

A

7 cervical, 13 thoracic, 6 lumbar, 4 sacral, 27-30 caudal

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57
Q

Describe the structure of the ribs in rats.

A

Ribs consist of ventral calcified and dorsal ossified segments without true costal cartilages.

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58
Q

How many bones make up the carpus and the tarsus in the rat?

A

Carpus = 9, Tarsus = 8

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59
Q

Describe the pelvic and hind limb bone structure of the rat.

A

Pelvis is formed by ossa coxae, which articulate with the first two sacral vertebrae. Hind limb bones = femur, tibia, and fibula that articulates with the tibia proximally but is fused distally.

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60
Q

What is the dental formula of the rat?

A

2(I 1/1, C 0/0, PM 0/0, M 3/3)

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61
Q

Name the salivary glands of the rat.

A

The salivary glands are paired and include the parotid, submandibular, and the smaller sublingual glands.
The parotid glands are serous, have 3-4 lobes located ventrolaterally from the caudal border of the mandible to the clavicle.
The submandibular glands are mixed, situated ventrally between the caudal border of the mandible and the thoracic inlet.
The sublingual glands are mucous, at the rostral pole of the submandibular glands

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62
Q

Where is brown adipose tissue located in the rat?

A

Also called multilocular adipose tissue or the hibernating gland; located on the ventral and lateral portions of the neck and can be confused with salivary glands.

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63
Q

Describe the anatomic structure of the rat stomach.

A

Divided into two parts - forestomach (cardiac portion) is nonglandular & corpus (pyloric portion) is glandular. The limiting ridge (margo plicatus) separates the two portions, with the esophagus entering at the lesser curvature through a fold in the ridge.

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64
Q

Why can’t rodents vomit?

A

Do not possess many of the anatomical and neurological components required for a functional vomiting reflex

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65
Q

Describe the anatomy of the rat intestine.

A

Small intestine = duodenum (8 cm), jejunum (80 cm), ileum (3 cm); comma shaped cecum with thin walls and a prominent mass of lymphoid tissue in its apical portion; colon = ascending colon with prominent oblique mucosal ridges, and the transverse and descending portions with longitudinal mucosa folds.

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66
Q

How many lobes does the liver have in the rat?

A

4: median - which has a deep fissure for the hepatic ligament; right lateral - partially divided; left - large; caudate - small and surrouds the esophagus.
Rats do NOT have a gallbladder - the bile ducts from each lobe form the common bile duct, which enters the duodenum about 25mm from the pyloric sphincter.

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67
Q

Describe the pancreas of the rat.

A

Very diffuse and lobulated organ; darker color and firm consistency compared to surrounding fat; numerous excretory ducts fuse into two to eight large ducts that empty into the common bile duct.

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68
Q

What are the three classifications of diets for rats?

A

Natural-ingredient, purified, chemically defined.

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69
Q

What is the most commonly used type of diet in most research applications?

A

Natural-ingredient; The nutrient composition of this type of diet varies from batch to batch because of various factors (e.g., relative costs of grains, weather conditions, harvesting and storage conditions, and concentrations of contaminants).

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70
Q

What type of diet is used for toxicological and other types of GLP studies?

A

Certified natural-ingredient diets. These are assayed and certified to not exceed maximum concentrations of a set list of contaminants (pesticides, heavy metals, mycotoxins, and estrogens).

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71
Q

Why are nutrient concentrations of purified diets less variable than natural ingredient diets?

A

Purified diets are made of defined ingredients, each composed of a single nutrient or nutrient class (e.g., casein, sugar, starch, vegetable oil, cellulose).
Downside = more expensive, often less palatable.

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72
Q

Name a frequently used purified rat diet.

A

AIN-76.

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73
Q

Describe chemically defined diets.

A

Formulated with very basically defined ingredients (e.g., specified amino acids, sugars, triglycerides, and essential fatty acids); often expensive and tend to be less palatable.

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74
Q

Name a dietary variable that can have significant impacts on both male and female rats.

A

Phytoestrogens.

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75
Q

List health benefits found to be associated with limit feeding (vs. ad lib feeding) in rats.

A

Increased longevity, reduction in incidence of neoplasia (e.g., lung, mammary, pancreatic islet, pituitary), reduction in chronic inflammation and fibrosis of the heart, reduction in acute inflammation of the prostate, reduction in radiculoneuropathy and acinal hyperplasia of the mammary gland.

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76
Q

What four pathways have been implicated to be involved in the caloric restriction effects on rodent health?

A

Insulin-like growth factor (IGF-1)/insulin signaling pathway, sirtuin pathway, adenosine-monophosphate (AMP)-activated protein kinase (AMPK) pathway, and the target of rapamycin (TOR) pathway.

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77
Q

What is the vaginal plate?

A

In the rat, the vagina is closed at birth by compact epithelium known as the vaginal plate. It begins to degenerate and cornify at 20-35 days of age and the canal is completely open between 40-80 days of age.

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78
Q

What clinical conditions can be seen with persistence of the vaginal plate?

A

Fully imperforate vagina or a vaginal septum. These conditions may be associated with infertility or metritis.

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79
Q

What anatomic changes can be used as signals of impending puberty in female and male rats?

A

Female = vaginal opening. Male = Balano-preputial separation

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80
Q

When does puberty occur in rats?

A

2-3 months old (significant variation between strains)

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81
Q

True/False. In rats, estrus occurs before full reproductive competency is reached.

A

True.

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82
Q

How long is the estrus cycle in rats?

A

4-5 days. Occurs year-round, including post-partum. ~1 day in each of the four stages. Cycles of up to 6 days are not uncommon.

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83
Q

How can the uterus appear in the proestrus in the rat?

A

Can appear “ballooned” with fluid; do not mistake for hydrometra.

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84
Q

When does ovulation occur in the rat?

A

~8-11 hrs after onset of estrus, usually between midnight and 2 am.

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85
Q

How long do ova remain viable in the rat?

A

10-12 hr.

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86
Q

When do testes descend in male rats?

A

~15 days of age.

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87
Q

When are sperm first produced and when does puberty occur in male rats?

A

Sperm production = 45-46 days of age. Puberty = 62-65 days. On histology, young rat testes show more degenerative germ cells prior to 75 days of age than afterward, indicative of poor efficiency of spermatogenesis at early ages in rats.

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88
Q

When during the dark cycle does coitus most commonly occur in rats?

A

Later in the dark cycle (rather than earlier)

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89
Q

What is ejaculatory latency?

A

Multiple intromissions (5-15), each lasting 0.3-0.6 sec and with two to nine pelvic thrusts precede the first ejaculation, which lasts about 1 sec. This first series of intromissions is called the ejaculatory latency and lasts about 10 min followed by a refractory period. Multiple series of intromissions and ejaculation, usu ~7, occur with increasing refractory periods between successive episodes.

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90
Q

When does implantation of the blastocyst occur in rats?

A

Between 5 to 7 days after fertilization the blastocyst implants in the endometrium; represents a process that takes 12-24 h to complete.

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91
Q

What is the gestation period in rats?

A

21-23 days, but can be as short as 19.

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92
Q

What are indications of estrus in the rat?

A

Ear quivering when back or head are stroked, lordosis when pelvic area stimulated, swelling of vulva, vaginal wall appears dry due to cornification of the vaginal epithelium

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93
Q

What percent of vaginal epithelial cells are cornified during estrus in the rat?

A

25-100%

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94
Q

Describe role of an impedence meter in detection of estrus in rats.

A

Changes in vaginal fluids and cytology also change the electrical impedance of the vagina during estrus. An impedence meter can be used to measure this with a probe inserted into the vagina. However, the impedence meter gives less info than cytology regarding the specific phase of estrus and the physical stimulation of the probe may induce pseudopregnancy.

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95
Q

When can pregnancy be detected in the rat?

A

Palpation = 10 days, esp accurate after 12 days.
Transabdominal ultrasound = 9-10 days
Doppler = fetal heartbeat can be detected by 12 days
Mammary gland and nipple development = 14 days

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96
Q

What effect does constant light have on estrous in rats?

A

Persistent estrus and cystic ovarian follicles without the formation of corpora lutea. Chronic exposure to even low intensity light during the dark cycle can result in early vaginal opening and ovarian atrophy.

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97
Q

What effect does caloric restriction have on estrous in rats?

A

15-30% restriction from ad lib can cause cessation of estrous cycles and delayed sexual maturation.

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98
Q

What effect can high ambient temperatures have on male rat fertility?

A

Can result in male infertility by causing irreversible degeneration of the seminiferous epithelium. Damage may occur in rats as young as 4 days and at temps as low as 26.6 C.

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99
Q

How long is average parturition in the rat?

A

1.5-3 hours.

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100
Q

Which litter in rats is usually the largest?

A

The second litter.

After 9 months of age, litter size if further decreased and the pregnancy rate declines after 12 months of age.

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101
Q

What is pregnancy wastage?

A

Loss of festuses. Occurs as a function of age. Primarily due to preimplantation and early posimplantation mortality. Can also be caused by maternal stressors (ex: earthquake, strenuous exercise; shipping?)
Maternal behavior in virgin rats enhanced at 19-20 months of age vs. 3-4 months of age.

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102
Q

Describe a newborn rat.

A

Altricial and nidicolous; hairless and blind; poorly developed limbs, short tails, and closed ear canals.
Inverse relationship between fetal weight and litter size.

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103
Q

What factors influence birth weight in rats?

A

Litter size, maternal age (pups of dams mated at 105 d weighed more than pup of dams mated at 35 or 70 d).

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104
Q

Describe the development of hearing in rats.

A

Cochlea and organ of Corti are immature at birth but develop to approx. adult morphology by weaning. First able to hear around 9 days old, but able to vocalize from birth.

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105
Q

Describe tooth eruption in rats.

A

Incisors erupt 6-8 days of age, molar 1 day 16, molar 2 day 18, molar 3 day 32-34.

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106
Q

Describe development of sight in rats.

A

Retina poorly developed at birth, equivalent to 4-5 month human fetus. Eyelids open at 14-17 days of age. Retina fully matures by 30-40 days of age. Final components of the angle of the anterior chamber not fully formed until 60 days of age.

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107
Q

Describe development of hair in rats.

A

Some hairs may be present on trunk at birth - usually associated with touch domes, indicating they are guard hairs. Pups fully haired at 7-10 days of age.

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108
Q

How is maternal antibody transferred to rat pups?

A

Transferred passively across the yolk sac in utero. CAn also be transferred across the intestinal mucosa from colostrum and milk to suckling rat. Transfer occurs at low rates shortly after birth, reaches maximal rates at day 14, and ceases by 21 days when gut closure said to be complete.

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109
Q

Describe the process for sex determination in preblastocyst rat embryos.

A

Males embryos cease development when exposed to antibody to the HY antigen, an resume development only after antibody washed off. 80% of embryos that developed into embryos in presence of the HY antibody produce female pups.

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110
Q

How can PCR determine sex of rat embryonic tissues?

A

PCR primers for sequences of the male sex determining region Y (SRY).

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111
Q

When does the micturition reflex mature in rat pups?

A

15 days of age.

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112
Q

Describe some way to sychronize estrus in female rats.

A

1) Administration 40 micrograms of luteinizing hormone releasing hormone agonist (LHRH) to mature female rats & can be bred 4 days later.
2) Administration of 40 mg methoxyprogesterone in the drinking water for 6 days in 200 ml ethanol/liter water, prepared fresh daily), followed by IM injection with 1 IU pregnant mare’s serum

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113
Q

Describe recommended steps for sperm collection in rats.

A

Semen from electroejaculation rapidly coagulates due to contributions of seminal vesicles and coagulating glands.
For AI or cryopreservation, instead collect sperm during terminal dissection. Sperm from the proximal portion (head) of the cauda epididymis are reported to have greater fertility than from middle or caudal portions.

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114
Q

What agents are used for hormonal superovulation in rats?

A
  1. Pregnant mare serum gonadotropin (PMSG) followed by human chorionic gonadotropin (HCG); similar to mice
  2. Follicle stimulating hormone (FSH) with or without luteinizing hormone (LH)
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115
Q

What technique can be used to rescue or maintain strains that do not have motile spermatozoa?

A

Intracytoplasmic sperm injection (ICSF) - IVF technique of microinseminaton of individual oocytes. By adding exogenous DNA, can also be used as a method for producing transgenic rats.

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116
Q

Which rat strains are generally more docile?

A

Sprague-Dawley background (CD or SC stocks) and Lewis generally more docile than Brown Norway or F-344 rats.

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117
Q

What is the typical frequency of rat alarm calls?

A

22 kHz (can be produced during handling)

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118
Q

Why do rat pups vocalize in the ultrasonic range?

A

To signal to their mothers before their ears are sufficiently developed for them to be capable of hearing.

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119
Q

When do female rats typically have a a shorter tail flick response?

A

Female rats have shorter tail flick response times in the middle of the dark period, as well as during estrus and metestrus.

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120
Q

What housing choices have rats shown preference for?

A

Solid flooring, bedding consisting of large particles of aspen wood chips, and nest boxes.

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121
Q

Streptococcal pulmonary disease - causative agent

A
Streptococcus pneumoniae (alpha-hemolytic)
Numerous serotypes - infection usu assoc. w/ more pathogenic serotypes 2, 3, 8, 16, 19.
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122
Q

Transmission of S. pneumoniae?

A

Natural host is humans. Transmission primarily via aerosol, fomites may play minor role.

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123
Q

Clinical signs of S. pneumoniae?

A

Usually asymptomatic and colonizes rat’s nasopharynx. Rat is used as a model of human infection, but immunosupression, neutropenia, or other special techniques usu needed to induce clinical disease. Clin dz = suppurative inflammation spreads to lungs, bronchopneumonia; sometimes fibrinosuppurative pleuritis; may become bacteremic and develop fibrinous inflammation of other serous surfaces (peritoneum, synovium) and other tissues.

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124
Q

How to monitor for S. pneumoniae infection?

A

Nasopharyngeal culture on blood agar.

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125
Q

What is the role of optochin inhibition in diagnosing S. pneumoniae?

A

Used to differentiate S. pneumoniae from other alpha-hemolytic streptococci; optochin inhbition is greater for most S. pneumoniae than other species.

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126
Q

What is optochin inhibition?

A

Ethylhydrocupreine hydrochloride (optochin), is a quinine derivative. Optochin selectively inhibits the growth of Streptococcus pneumoniae at very low concentration (5 mg/mL or less). Optochin may also inhibit viridans streptococci, but only at much higher concentrations.

Optochin is water-soluble and diffuses readily into agar medium. Filter paper disks impregnated with optochin can be used in a disk diffusion test.

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127
Q

Does a PCR positive for S. pneumoniae indicate a health concern?

A

Not necessarily. S. pneumoniae may be detected from PCR of nasopharnyx or lung, but there are nonpathogenic isolates. Need to confirm with histopath. Isolation of S. pneumoniae from asymptomatic rats is not necessarily a colony health threat.

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128
Q

What is the recommended control strategy for S. pneumoniae in a rat colony?

A

Action to eliminate only indicated in presence of characteristic lesions or detection of known pathogenic serotypes - depopulation and restock from an SPF source.

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129
Q

Is asymptomatic carriage in rats of S. pneumoniae detrimental for research studies?

A

Physiologic variability associated with asymptomatic carriage has not been reported.

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130
Q

How are beta-hemolytic streptococci divided into groups?

A

By Lancefield antigens. Lancefield groups B and G most commonly isolated from rats.

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131
Q

When have beta-hemolytic streptococci been associated with disease in rats?

A

Only in one case of naturally occurring dz - a Group B streptococci was linked to myocarditis and abscesses in 21-24 day old pups of a Munich Wister-Frömter line transgenic for human diphtheria toxin.
Exclusion of beta-strep from rat colonies is neither necessary nor practical; human are often carriers.

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132
Q

What is streptococcal enteropathy?

A

Cause by nonhemolytic (gamma-hemolytic) Lancefield group D enterococci, including Enterococcus hirae, E. faecium-durans 2, and E. faecalis 2. Affects only suckling rats, not postweaning animals. Affected litters have diarrhea or soft stool that is bright yellow & pasty. Mortality can be high. Villi of small intestine are carpeted with G(+) cocci. Pathogenic isolates involved have the ability to adhere to the surface of microvilli

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133
Q

What are autochthonous flora?

A

Microorganism native to the host environment. Some Enterococcus spp. have been considered autochthonous flora in the rat.

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134
Q

How can streptococci be excluded from rat housing?

A

Aseptic microisolator technique or by use of isolators. Low incidence of disease may not warrant the additional time and expense to do this.

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135
Q

What is the etiologic agent of pseudotuberculosis in rats, mice, guinea pigs, and hamsters?

A

Corynebacterium kutscheri. G(+) coryneform (club-shaped); found in soil, sewage, and marine environments. In guinea pigs and hamsters there has only been bacterial evidence, but no disease reported.

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136
Q

What is the route(s) of transmission for Corynebacterium kutscheri?

A

Direct contact or oronasal exposure.

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137
Q

What are the clinical signs of Corynebacterium kutscheri?

A

Usually clinically silent. Advanced dz may have non specific signs - ruffled fur, hunched, dyspnea and rales, porphyria, mucopurulent ocular & nasal discharge, lethargy, lameness; usu followed by death in 1-7 days.

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138
Q

What are the gross pathology lesions of Corynebacterium kutscheri?

A

Solitary or multiple randomly distributed abscesses due to septic emboli getting stuck in organs/tissues with extensive capillary networks - lung, liver, kidney, joints. LUNG most frequently involved in rats. Suppurative inflammation in the preputial gland and tympanic bullae.

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139
Q

What are the histopathology lesions of Corynebacterium kutscheri?

A

LUNG - interstitial inflamm d/t hematogenous seeding; suppurative exudate in bronchi and bronchioles; caseous necrosis common, epitheliod macrophages and multinucleated giant cells may be present in abscesses.
LIVER - large areas of caseous necrosis
KIDNEYS - septic embolic glomerulitis, abscesses with or without pyelonephritis
Abscesses and caseous necrosis in virtually any tissue.

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140
Q

How is Corynebacterium kutscheri diagnosed?

A

Definitive dx = culture or PCR; sampling sites include submaxillary (cervical) lymph nodes, oropharynx, nasopharynx, middle ears, preputial glands, feces.
Oral cavity, cecum, colon, and rectum may harbor organism.
Microscopic evaluation of lesions - irregularly branching arrays of G(+) rods in tissue sections or impression smears.
Serology - can have false positives or false negatives.

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141
Q

What is the best diagnostic sampling site for Corynbacterium kutscheri in rats?

A

Other than direct lesions, submaxillary (cervical) lymph nodes.

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142
Q

What factors can trigger latent infections of Corynebacterium kutscheri to become clinical?

A

Stressors that cause immunosuppression - poor husbandry, overcrowding, shipping, malnutrion, intercurrent infections, irradiation, immunosuppressive drugs.
Increasing age - disease is more frequent in older animals.

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143
Q

What are differential diagnoses for multiple abscesses in rats?

A

Streptococcosis, streptobacillosis, mycoplasmosis (pulmonary abscesses), cilia-associated respiratory (CAR) bacillus (pulmonary abscesses).
Of these, ONLY CAR bacillus and mycoplasmosis would be found predominantly in older animals.

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144
Q

What tissue conditions are preferred for PCR to check for Corynebacterium kutscheri?

A

Fresh or frozen tissue are preferred to formalin-fixed paraffin-embedded tissue.

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145
Q

What are prevention strategies for Corynebacterium kutscheri?

A

Rederivation and bioexclusion.

146
Q

What are research complications associated with Corynebacterium kutscheri?

A

Morbidity/mortality can disrupt studies, most likely to occur in immunocompromised rats.

147
Q

What causes Tyzzer’s disease?

A

Clostridium piliforme

148
Q

What is the host range of Clostridium piliforme?

A

Many mammals including numerous rodent species, rabbits, carnivores, horses, NHP, humans

149
Q

How is Clostridium pilforme transmitted in rats?

A

Spores through fecal-oral. Spores are highly resistant to dessication and some disinfectants (delicate vegetative form survives only in cells).
Spores ingested - produced vegetative form that is phagocytosed by mucosal epithelial cells covering gut-associated lymphoid tissue, or Peyer’s patches

150
Q

What are clinical signs of Clostridium piliforme in rats?

A

Usually no clin signs; overt dz in many species most likely in young, recently weaned animals - anorexia, lethargy, emaciation, ruffled fur, acute death without clin signs, diarrhea w/ mucus and blood, abdominal distension (rare sign)

151
Q

What are the gross pathologic lesions of Clostridium piliforme in rats?

A

Multiple pale foci of necrosis in the liver; megaloileitis (dilated, flaccid, hyperemic ileum); hyperemia, edema, hemorrhage, ulceraton of intestine esp. terminal ileum, cecum, colon; enlarged, hyperemic, edematous mesenteric LNs; myocardial necrosis (pale linear streaks esp at apex of heart).

152
Q

What are the histopathologic lesions of Clostridium piliforme in rats?

A

Necrotizing enteritis, typhlitis, colitis; coagulative necrosis of liver with moderate leukocytic infiltrate (neutrophils and mononuclear cells) at lesion periphery; lesions may be hemorrhagic with mineralization over time; myocardial degeneration & necrosis w/ mixed leukocytic infiltrate and dystrophic calcification.

153
Q

How is Clostridium piliforme diagnosed in rats?

A

Histopath - diagnostic if bacilli seen - vegetative form is G(-), filamentous, intracellular bacilli 8-20 µm long x 0.3-0.5 µm wide - jumbled, “pickup stick” arrangement.
Serology - subject to false (+)s; “stress tests” to exacerbate latent infx followed by serology efficacy is questionable
Sentinels on dirty bedding - need to be same species to avoid species specificity related false (-)s
PCR - fecal samples but will only detect animals that have not cleared infx; liver lesions

154
Q

What histopath stains facilitate visualization of Clostridium piliforme in tissues?

A

Warthin-Starry silver stain (best)
Giemsa (useful for liver lesions)
Methylene blue
(Stains POORLY on Gram stain)

155
Q

In what tissues can Clostridium piliforme be found on histopath?

A

Liver - in surviving hepatocytes at periphery or within lesions
Intestine - within mucosal epithelial cells or mucosal crypts (normal flora may make hard to find); in tunica muscularis of small instesting
Heart - in cardiac myocytes

156
Q

What are differential diagnoses for Clostridium piliforme in rats?

A

Diff dx for necrotizing hepatitis: bacterial septicemias like Corynebacterium kutscheri; rat virus

157
Q

How is Clostridium piliforme controlled in rat colonies?

A

Exclusion techniques
B/c spores resistant - cross-contamination from conventional of wild-caught colonies could be more likely & very thorough disinfection is needed after an outbreak

158
Q

What are potential research complications of Clostridium piliforme?

A

Morbidity & mortality; effects of coagulation and leukokines has been reported in mice w/ subclinical infx

159
Q

What causes pasteurellosis in rats?

A

Pasteurella pneumotropica - G(-) coccobacillus; grows aerobically on sheep blood agar, non-hemolytic, smooth gray or yellow translucent colonies.

160
Q

What is the host range of Pasteurella pneumotropica?

A

Numerouds mammalian species, including humans

161
Q

What tissues is Pasteurella pneumotropica isolated from in rats?

A

High prevalence in infected colonies; isolated most often from nasopharynx, cecum, vagina, uterus, conjunctiva

162
Q

What are clinical signs of Pasteurella pneumotropica in rats?

A

Most animals asymptomatic; rare conjunctivits, metritis, mastitis. On histo - lesions characterized by necrosuppurative inflammation

163
Q

How is Pasteurella pneumotropica diagnosed in rats?

A

Culture - of nasopharynx, cecum, vagina, uterus, conjunctiva

PCR - feces, oral swabs, dust from IVC plenums or other animal air spaces

164
Q

How is Pasteurella pneumotropica prevented and controlled in rats?

A

Control may not be necessary in immune competent animals b/c clinical disease is very rare.
Enrofloxacin has been described as tx in mice.
Rederivation by C-section or embryo transfer effective to eliminate - offspring held in strict isolation until confirmed negative

165
Q

What is the risk of reinfection with Pasteurella pneumotropica?

A

Little risk - not transmitted significantly by fomites, does not persist or multiply in environment, very rarely colonizes humans

166
Q

What are research complications of Pasteurella pneumotropica?

A

Studies involving tissues/organs affected by inflammaton would be affected

167
Q

What Salmonella species is most common in rats?

A

Salmonella enterica; compromises more than 2500 serovars - vary greatly in pathogenicity ad geographic distribution

168
Q

How is Salmonella enterica transmitted?

A

Ingestion of contaminated materials - feed, bedding, water; incursion of wild or feral rodents into a lab facility poses further risk.

169
Q

What are clinical signs of Salmonella enterica in rats?

A

Clinical signs are rare in rats; hunched posture, ruffled fur, lethargy, weight loss, conjunctivitis, less often soft stool and diarrhea

170
Q

What are histopathologic changes in rats with Salmonella enterica clinical disease?

A

Mural thickening and mucosal ulcers in cecum and ileum; splenomegaly; enteric lesions characteized by edema of lamina propria, leukocyte infiltration in areas of ulceration, reactive hyperplasia of crypt epithelial cells; lymphoid hyperplasia w/ focal necrosis & neutrophils in Peyer’s patches, spleen, and mesenteric LNs
Septicemia - spleen and liver necrosis, with emboli of fibrin, bacteria, and debris present in liver, spleen, and LNs

171
Q

How is Salmonella enterica diagnosed in rats?

A

Culture - feces, mesenteric LNs, liver, spleen, blood; material placed in enrichment broth & inoculated on selective growth media; symptomatic animals should be culture (+) but an infected colony can have only a low incidence of asymptomatic carriers - detection may require repeated testing & unknown if PCR would find a higher rate of carriage than culture
PCR - feces, mesenteric LNs, liver, spleen, blood

172
Q

What are differential diagnoses for Salmonella enterica in rats?

A

Tyzzer’s disease, rotavirus, enterococcal enteropathy, cryptosporidiosis, problems with feed/water

173
Q

What is the prevention strategy for Salmonella enterica in rat colonies?

A

Rigorous pest control, ensuring feed and bedding is not contamined, good personal hygiene of employees so they are not a source of Salmonella

174
Q

How is Salmonella enterica controlled in a rat colony?

A

All animals destroyed, all surfaces and materials sterilized or discarded; strict quarantine of a small number of animals (flexible film or semirigid isolator) my be practical prior to rederivation by C-section or embryo transfer.
Treatment NOT recommended, b/c a chronic carrier state may result.

175
Q

What are research complications of Salmonella enterica in rats?

A

Infx rats should not be used for research b/c ZOONOTIC & can infx other animals

176
Q

What causes pseudomoniasis in rats?

A

Pseudomonas aeruginosa - G(-) bacillus in order Eubacteriales, family Pseudomonadaceae

177
Q

How is Pseudomonas aeruginosa transmitted?

A

Pseudomonas aeruginosa is motile, aerobic, oxidase-positive; widely distributed in water, soil, sewage, & skin and GI tract of many animals; commensal flora of humans, domestic animals, and lab rodents; isolation frequency increases in animals and humans receiving antibiotics

178
Q

What are clinical signs of Pseudomonas aeruginosa in rats?

A

Considered of low significance in rats - should be suspected in irradiated rats or those tx with radiomimetic agents that die earlier than expected
Rarely causes dz except in animals with severe host deficits, esp deficient functional phagocytes (macrophages, neutrophils, and their serum opsonins)
Athymic nude mice NOT subject to high incidence unless irradiated or treated with myelosuppressive agents

179
Q

What are gross pathology and histopathology findings of Pseudomonas aeruginosa in rats?

A

From infx via indwelling jugular catheter - septicemia w/ vegetative valvular endocarditis, multifocal hemorrhagic pneumonia; fibrin emboli, leukocytes, and G(-) bacteria observed in the heart, lungs, and occasionally other organs

180
Q

How is Pseudomonas aeruginosa diagnosed in rats?

A

Culture - will grow on blood agar, but isolation enhanced by selective media like Pseudomonas isolation agar, or Pseudomonas agar P; selective media helpful as only low numbers of organisms may be harbored in common sites for isolation - cecum & nasopharynx
PCR
Be careful of significance of (+) results d/t ubiquitous nature of P. aeruginosa

181
Q

How is Pseudomonas aeruginosa prevented in rat colonies?

A

Exclusion of P. aeruginosa rarely justified b/c requires gnotobiotic methods; sterilization of all water; sterilization of cages, feed, and bedding; prevention of all human skin or wet surface contact

182
Q

How are Pseudomonas aeruginosa infections controlled in rats?

A

Watering system - P. aeruginosa forms biofilms, usually with reduced metabolic activity, embedded in a dense glycocalyx - bacteria in a biofilm are very resistant to chlorine and monochloramine & may be inaccessible to abx; chlorination can sig reduce colonization of mice but will not eliminate infx
Rederivation by C-section or embryo transfer required to eliminate from colony
Gentamycin in drinking water (1 g/L) has eliminated in mice, but not practical for large rat groups

183
Q

What are potential research complications of Pseudomonas aeruginosa?

A

Infx through indwelling catheters possible; could interfere with radiation studies or those using strains with specific immune deficits

184
Q

What is the significance of Streptobacillus moniliformis in rat colonies?

A

One cause of rat-bite fever; now virtually nonexistent in modern lab aimals
G(-) pleumorphic bacillus, will grow nonhemolytically on sheep blood agar but trypticase soy agar enriched with 20% horse serum is preferred

185
Q

What is the significance of Streptobacillus moniliformis in wild rats?

A

Commensal in wild rats; inhabits nasopharynx, middle ear, and respiratory tract; present in blood and urine
Transmitted to humans by bites, aerosols, and fomites
Non pathogenic in rats; in humans has 3-10 day incubation period followed by fever, vomiting, arthralgia, and rash - tx with abx & mortality is low

186
Q

What are prevention strategies for Streptobacillus moniliformis in rat colonies?

A

Monitoring by PCR & culture of blood and nasopharyngeal swabs
Positive colonies should be immediately terminated
Detection in a lab rat colony would indicate close range exposure to infected wild rats

187
Q

List Helicobacter spp. that are natural infections in rats.

A

H. muridarum
H. trogontum (most prevalent of naturally occurring intestinal helicobacters in rats)
H. bilis (large bowel of immunodeficient rats)
H. pullorum (breeding colony Brown Norway rats housed in same room as infx mouse colony; persistent infx by oral inoculation of Brown Norway rats and Sprague Dawley rats)

188
Q

Describe features of helicobacters of rats.

A

Microaerophilic, G(-), flagellated bacteria; spiral, slightly curved, or straight; coccoid forms have been described for H. bilis and H. pylori

189
Q

What is the host range of Helicobacter spp.?

A

Not fully elucidated yet.
H. bilis - rats, mice, dogs
H. muridarum - rats, mice
H. pullorum - mice, rats, chickens, humans
H. trogontum - host range not reported yet
Many other Helicobacter spp. can colonize a phylogenetically wide range of hosts

190
Q

How are Helicobacter spp. transmitted in rats?

A

Presumed fecal-oral (as in mice; soiled bedding sentinel mice will only detect a subset of infx mice)
Only one study attempting transmission of H. pullorum through soild bedding; otherwise no studies published of transmission of naturally occurring Helicobacter in rats

191
Q

What are clinical signs of Helicobacter spp. in rats?

A

Infx typically lifelong; need to distinguish infection/colonization from disease
H. muridarum and H. trogontum may be nonpathogenic in rats. (H. muridarum reported to cause lymphocytic gastritis in mice, with loss of parietal cell mass leading to increased gastric pH)

192
Q

What are pathogenic factors of H. pylori?

A

Urease, vacA (a vacuolating cytotoxin), presence of a pathogenicity island

193
Q

What are pathogenic factors of other Helicobacter spp. in rats?

A

All enterohepatic Helicobacter spp. identified in rats are urease (+); other virulence factors have not been reported.

194
Q

What are pathologic lesions of Helicobacter spp. in rats?

A

H. bilis - in athymic nude rats - proliferative and ulcerative typhlitis, colitis, and proctitis; focal or diffuse thickening of cecal wall; cystic mesenteric LNs; crypt epithelium hyperplasia w/ cytoplasmic basophilia and reduced goblet cells, lamina propria infiltrated by lymphocytes, plasma cells, few eosinophils; cecum mucosal erosion and ulceration
No lesions reported in immunocompetent rats d/t any Helicobacter spp.

195
Q

What lesions in rats indicates that Helicobacter spp. should be a prime differential?

A

Proliferative lesions of the large bowel.

196
Q

How are Helicobacter spp. diagnosed in rats?

A

PCR - best; fecal pellets, fecal dust, cecal mucosal scrapings or tissue
Culture - greatly complicated by intestinal flora - can pass through 0.65 micron filter, then culture of Brucella agar w/ trimethoprim, vancomycin, & polymyxin to suppress growth of unwanted organisms; cultured considered less sensitive so interpret negative results cautiously

197
Q

What are prevention and control strategies for Helicobacter spp. in rats?

A

Tx - oral antibiotics several times daily or antibiotics in feed for small groups; 100% elimination from large groups less likely (even a single (+) rat can reinfect entire colony)
Cross-fostering pups has been reported successful in mice (not been reported in rats)
Rederivation by C-section or embryo transfer

198
Q

What are research complications of Helicobacter spp. infection in rats?

A

Research complications d/t Helicobacter spp. inf in rats have NOT been reported.

199
Q

What is the causative agent of CAR bacillus?

A

A ‘gliding bacteria’ (NOT genus Bacillus) - motile but without visible means for motility; may be related to Flavobacterium or Flexispira based on 16S rRNA sequencing
Has been identified in rats, mice, and rabbits

200
Q

How is CAR bacillus transmitted?

A

Primarily via direct contact with infected animals

Fomites likely not significant cause, does not transmit well in bedding, airborne exposure not impt

201
Q

What are clinical signs of CAR bacillus in rats?

A

Usually asymptomatic; may case weight loss, dyspnea

202
Q

What are gross lesions of CAR bacillus in rats?

A

May not always cause gross lesions
Transluent gray cystic lesions - representing dilated, mucus-filled airways - on the pleural surface
Suppurative bronchopneumonia, if coinfx w/ Mycoplasma pulmonis or other pathogens

203
Q

What are histopathologic lesions of CAR bacillus in rats?

A

Hyperplastic periobronchial and peribronchiolar mononuclear cell cuffs in the lungs
Thin basophilic layer may be on surface of airway epithelium with H&E staining - cilia are more basophilic than normal (but this is not specific for CAR bacillus)
Warthin-Starry or methenamine silver stain - filamentous bacilli among cilia of respiratory epithelium from nasal cavity to bronchioles
Upper resp tract involved earlier in infx than lower resp tract - include upper resp tract in sectioning!

204
Q

How is CAR bacillus diagnosed in rats?

A

Serology - there can be false (+); confirm (+) with Steiner stain of tracheal mucosal scraping or histopath with special stain
PCR - nasal swabs; may be (+) before serology; infx is lifelong & readily retrieve CAR bacillus from tracheal lavage or scraping
NOT transmitted well by soiled bedding - sentinels may not detect

205
Q

What are differential diagnoses for CAR bacillus in rats?

A

Murine respiratory mycoplasmosis, bacterial pneumonia (Streptococcus pneumoniae, Corynebacterium kutscheri, etc.), and viruses
Detection of CAR bacillus should raise suspicion of coinfx with other pathogens, esp Mycoplasma pulmonis

206
Q

How is CAR bacillus prevented and treated in rats?

A

Exclusion of infected animals for prevention.
NO effective tx - due to need for direct contact to transmit, may be able to ID animals by serology and cull or quarantine (+) animals, monitor (-) animals by PCR to control

207
Q

What are the research complications of CAR bacillus in rats?

A

Interference with research unknown. Interference with ciliary function suspected but not measured. In mice CAR bacillus incited antibody response and increased some serum and pulmonary cytokines (effect on resp and immune function in rats not reported)

208
Q

What is the causative agent of mycoplasmosis in rats?

A

Murine respiratory mycoplasmosis (MRM), as called chronic respiratory disease - caused by Mycoplasma pulmonis (infx is rare in N. America)

209
Q

How is Mycoplasma pulmonis transmitted in rats?

A

Horizontally by direct contact and aerosol; vertically by in utero transmission; venereal transmission may be possible

210
Q

What are clinical signs of Mycoplasma pulmonis in rats?

A

Clinical signs usually seen in older rats; clinically silent in young animals
Nonspecific rales, dyspnea, snuffing and chattering, ocular and nasal discharge, chromodacryorrhea, rubbing of eyes, head tilt; if severe middle ear involvement rat may spin when held up by tail; decreased reproductive efficiency

211
Q

What factors impact severity of mycoplasmosis in rats?

A

Animals age, strain, immune status, lymphreticular function, presence of other infx like Sendai virus
Vit A and E deficiency may exacerbate disease
Mycoplasma isolates vary in virulence
Environmental factors - intracage ammonia, temperature, humidity

212
Q

How does Mycoplasma pulmonis impact rats physiologically?

A

M. pulmonis possibly damages host cells (dysfunction or loss of cilia) - accumulation of exudate, opportunisitc bacterial infxs, and impaired transport of ova (infertility)
M. pulmonis competes for host cell nutrients and metabolites - may produce toxic metabolites like peroxides & nonspecific mitogens - mitogens may cause proliferation of autoreactive clones of lymphocytes
M. pulmonis evades host immune defenses, so infx and some lesion (esp in upper resp tract) are persistent and often progressive; mechanism of immune system evasion unknown

213
Q

What are gross lesions of mycoplasmosis in rats?

A

Suppurative rhinitis, otitis media, laryngitis, tracheitis; suppurative bronchopneumonia w/ or w/out atelectasis, bronchiectasis, and abscesses
Widespread bronchiectatic abscesses = COBBLESTONE lung appearance (usu endstage dz)
Arthritis, occasionally resorbed fetuses, suppurative salpingitis

214
Q

What are histopathology lesions of mycoplasmosis in rats?

A

Respiratory - suppurative exudate, hyperplasia (squamous metaplasia) of mucosal epithelium, severe hyperplasia of BALT (diff dx lymphoma), pseudoglandular hyperplasia of nasal epithelium in chronic cases, hyperplasia of peribronchial alveolar type II pneumoncytes; CAR bacillus & other secondary bacterial pneumonias common
Genital tract - suppurative oophoritis and salpingitis, hydrosalpingitis, chronic suppurative endometritis, pyometra

215
Q

How is mycoplasmosis diagnosed in rats?

A

Culture - exudate from upper resp tract and middle ears
PCR - respiratory samples
Serology - respiratory samples
Organism is sensitive to dessication, so unlikely to efficiently transmit to soiled bedding sentinels

216
Q

What are differential diagnoses for mycoplasmosis in rats?

A

Other bacterial pneumonias (CAR bacillus, Corynebacterium kutscheri, streptococcis), mycotic pneumonia, iatrogenic lesions due to oral gavage errors
Coinfx with viruses - Sendai virus, pneumonia virus of mice - common

217
Q

What are prevention and control strategies for mycoplasmosis in rats?

A

Prevention - high quality vendors, segregate clean colonies from conventional or wild rodents, quarantine and test imported rodents
Tx - tetracycline used historically to minimize symptoms and prolong survival but antimicrobial eradication unlikely
Control - depopulation and restocking; rederivation

218
Q

What are research complications of mycoplasmosis in rats?

A

Interferes with research of immune system, respiratory system, reproductive system; has also confounded the diagnosis of pulmonary lymphoproliferative disease in toxicology safety testing

219
Q

What is the causative agent of hemobartonellosis in rats?

A

Mycoplasma haemomuris (formerly Haemobartonella muris) - G(-) bacterium that parasitizes erythrocytes of rats; obligate parasite and cannot grow in vitro

220
Q

How is Mycoplasma haemomuris transmitted in rats?

A

Transmitted by the spiny rat louse (Polyplax spinulosa) - louse is very rare in modern lab animal facilities. Both the agent and the vector are still extant in N. America and presumably elsewhere, so low-level continuing threat

221
Q

What are clinical signs of Mycoplasma haemomuris in rats?

A

Clinical signs typically only occur if normally latent infection is activated by immunosuppression or splenectomy
Weight loss, hemoglobinuria, pallor, dyspnea
Clin path - anemia, reticulocytosis, increased coagulation times, decreased plasma proteins, increased serum immunoglobulins (IgG, IgM)

222
Q

What are pathology lesions of hemobartonellosis in rats?

A

Only see lesions if active infection - anemia, hemoglobinuria, splenomegaly; possibly parasitemia on blood films during active infection

223
Q

How is hemobartonellosis diagnosed in rats?

A

Should be suspected any time lice are found in a rat colony or when anemia and hemoglobinura are observed
Dx - detection of organism in RBCs - round (coccoid), elongate (rod), or dumbbell-shaped densities on the erythrocyte surface

224
Q

How is hemobartonellosis prevented and controlled in rats?

A

Prevention - exclusion of Polyplax spinulosa, control biologic materials introduced into colony
Control - rederivation by embryo transfer or C-section; tx w/ antirickettsial compouns (tetracyclines, arsenicals) may be appropriate for small groups

225
Q

What are research complications of hemobartonellosis in rats?

A

Reduces half-life of erythrocytes, can alter function of the mononuclear phagocyte system, can increase rejection of transplantable tumors, interfere with blood-borne parasitic disease research (malaria, trypanosomiasis)

226
Q

What is the taxonomy of Sendai virus?

A

RNA virus; Family Paramyxoviridae, Genus and Species Respirovirus - this species contains strains that are antigenically homologous

227
Q

How is Sendai virus transmitted between rodents?

A

Through the respiratory tract by aerosol or direct contact; highly contagious

228
Q

What are clinical signs of Sendai virus in rats?

A

Usually symptomatic and self-limiting in rats.
Can cause reduced production and litter sizes, retarded growth of young; rarely clinical respiratory signs
Co-infection with Mycoplasma pulmonis, CAR bacillus, Pasteurella pneumotropica, and pneumonia virus of mice (PVM) increases severity of clinical disease and pulmonary lesions

229
Q

What is the major site of antibody production to Sendai virus in rats?

A

Lewis rats inoculated intranasally showed that draining LNs of the upper respiratory tract are the initial and major site of antibody production
Development of IgG antibodies coincides with clearance of resp tract infx and recovery

230
Q

What are pathology lesions of Sendai virus in rats?

A

Rhinitis - focal to diffuse necrosis of epithelial cells, leukocytic infiltrate w/ neutrophils, lymphocytes, and plasma cells
Hyperplastic to suppurative bronchitis to focal alveolitis - alveolar septa hypercellular with infiltrate of alveolar macrophages, neutrophils, lymphocytes
Later in dz - perivascular and peribronchial cuffing with lymphocytic and plasmacytic infiltrate that may remain 7 mths after infx

231
Q

Where does Sendai virus replication occur in rats?

A

In bronchial epithelial cells, type I & type I pneumocytes, and alveolar macrophages

232
Q

Which rat strains have more severe lesions to Sendai virus?

A

Brown Norway & LEW rats (more severe than in F-344 rats)

233
Q

How is Sendai virus diagnosed in rats?

A

Multiplex fluorescent immunoassay (MFIA or MFI) - test of choice; more sens and spec than ELISA & require less serum
IFA, Western blot - to confirm MFIA results
PCR - trachea and lung samples for active infection

234
Q

How is Sendai virus prevented in rat colonies?

A

Serology of colonies; PCR testing of biologic materials (tumors, cell lines)
NOT well detected by soiled bedding sentinels

235
Q

How is Sendai virus controlled in rat colonies?

A

‘Burnout’ technique: Neutralizing antibody in immunocompetent rats will render infx self-limiting - if antibody-naive rats are not introduced and pregnant and preweanling rats culled and breeding halted, virus will be eliminated form colony in 4-8 weeks, presuming ALL rats in colony have been exposed or that further interindividual transmission is prevented so no new infections occur

236
Q

What are research complications of Sendai virus in rats?

A

Respiratory tract interference; may modulate immunological responses (e.g., reduce severity of adjuvant arthritis, and depress T cell and thymocytotoxic autoantibody)

237
Q

What is the etiologic agent of rat coronavirus?

A

Family Coronaviridae, Genus Betacoronavirus, species murine coronavirus - contains secveral distainct serotypes incl. murine hepatitis virus and rat coronaviruses
Two prototype coronaviruses in rats are Parker’s rat coronavirus (RCV-P) and sialodacryoadenitis virus (RCV-SDA) - clin signs can be similar & defining the neutralization group of a new RCV isolate is NOT useful in predicting its pathogenic potential

238
Q

Do neutralizing antibodies to one rat coronavirus prototype offer cross protection to other virus strains?

A

NO - neutralizing antibodies to one prototype will not offer significant cross protection to other strains, thus allowing viral shedding and recurrence of clinical signs and lesions, albeit diminished

239
Q

How are rat coronaviruses transmitted?

A

Direct contact with infected rats, aerosol, fomites

240
Q

When are rats susceptible to reinfection with rat coronavirus?

A

Virus present in target tissues for about 1 week - heightened antibody levels at this time render the infection self-limiting but immunity is NOT lifelong (can be susceptible to reinfx as early as 6 mths after initial infx & able to transmit to naive rats)
Severity of lesions during reinfx is minimal compared with primary infection

241
Q

What are clinical signs of rat coronavirus?

A

Asymptomatic or transient clinical (sialodacryoadenitis) assoc w/ tissue tropism for salivary glands, lacrimal glands, Harderian glands, and respiratory epithelium

1) Endemic infx in breeding colony where mature animal are immune = preweanling, nonimmune rat conjunctivitis (signs last about 1 wk)
2) Sudden clinical signs in naive postweanling-to-adult rats w/ cervical swelling due to inflammation and edema of submaxillary salivary glands, nasal and ocular discharges, porphyrin staining, photophobia, corneal opacities, corneal ulcers (signs last less than 2 wks); some animal may have chronic ketatitis and megaloglobus

242
Q

What are pathologic changes associated with rat coronavirus?

A

Rhinitis, tracheitis, focal bronchitis due acute dz w/ mononuclear and polymorphonuclear cell infiltration, hyperplastic respiratory epithelia with loss of ciliated surfaces, focal alveolitis - lesions in lower resp tract abate in 7-10 days, those in nasopharyx rmain longer
Histo changes with sialodacryoadenitis (SDA) - coagulation necrosis of ductal and acinar epithelial cells in salivary and lacrimal glands in acute stage; squamous metaplasia during reparative period starting at 7-10 days w/ mixed leukocyte infiltrate; regeneration of epithelial cells occurs in about 4 wks postinfx; focal lesions may persist longer in Harderian glands

243
Q

How is rat coronavirus diagnosed?

A

Antibodies are produced about 7 days after infx - then can use serology for MFI with confirmatory IFA or Western Blot
Histo exam of the Harderian glands, submaxillary and parotid salivary glands
PCR of infected glands

244
Q

What are differential diagnoses for rat coronavirus?

A

Mycoplasma, Sendai virus, stress-associated factors the induce chromodacryorrhea
Rat coronavirus is readily detectable by dirty bedding sentinels due to its infectivity

245
Q

How is rat coronavirus prevented in lab colonies?

A

Prevent entry of infected rats and wild rats

246
Q

How is rat coronavirus controlled in lab colonies?

A

Based on fact that rats only shed virus for ~1 week & are then immune; virus NOT transmitted vertically

  • Allow virus to spread through room and prevent entry of susceptible rats; suspend breeding and removal of preweanlings; provide ~6-8 week period then shedding should be done and susceptible rats can be brought into room
  • If breeding cannot be suspended - define subset of breeding colony that is seropositive, relocate these to a separate room, allow litters to be born in the original colony until the relocated breeders are in late gestation and then cull original colony
247
Q

What are potential research complications of rat coronavirus?

A

Complications reflect tropisms for lacrimal and salivary glands, vomeronasal organ, respiratory epithelium; exposure keratitis from lack of tear production; exophthalmos due to edema of Harderian gland
Except for long-term ocular lesions, complications with research expected to be linked to 2-3 week period of active infx - food intake decreased d/t cervical swelling
Can impair nerve regeneration

248
Q

What is the etiologic agent of rat parvovirus?

A

Parvoviruses - ssDNA virus w/ predilection for mitotically active hose cells
Parvoviruses that infx rats incl. (Kilham’s) rat virus (RV). (Toolan’s) H-1 virus, rat parvovirus (RPV), rat minute virus (RMV)
The above viruses, plus minute virus of mice and mouse parvovirus are all ONE SPECIES - Rodent protoparvovirus 1
RV initially isolated from a transplantable tumor
H-1 initially isolated from a tumor cell line passed in rats
Rat parvovirus originally called rat orphan parvovirus (OPV)

249
Q

How is rat parvovirus transmitted?

A

Excreted in urine and milk, aerosol transmission through direct contact or fomites, contamined bedding (RV contaminted bedding stored at room temp for 5 wks could seroconvert rats for 5 wks)
Rats may harbor and transmit RV long after seroconversion - strain-dependent
Infx of pregnant females results in persistent infx of pups; pups of persistently infected dams are presumably protected by maternal antibody
DNA and antigenic evidence of RV most likely in lymphoid tissues, endothelium, vascular muscle tunics, renal tubular epithelium

250
Q

What are clinical signs of rat parvovirus?

A

Primarily subclinical; clinical signs are sporadic, usu seen in preweanling litters - reduced litter size, runted litters, fetal and neonatal death
One outbreak of young adult rats reported with hemorrhage and necrosis of the brain, testes, and epididymides
Ability of RV to cross the placenta depends on virus strain, dose, and time of gestation

251
Q

When does resistance to lethal rat parvovirus infection develop?

A

During the first postpartum week

252
Q

What pathology is associated with rat parvovirus?

A

Correlation of age and RV pathology thought to be due to decreased complement of target cells in S-phase of division
Immune competent rats mount a classic Th1 immune response - results in viral clearance
Atyhmic rats have more severe and persistent infx than euthymic rats

253
Q

How is rat parvovirus diagnosed?

A

Serology - recombinant capsid viral protein (VP2) antigens of each parvovirus along with a recombinant nonstructural protein (NS1) antigen (latter is shared among parvoviruses)
PCR - RV, H-1, RPV, RMV assays available - tissue, feces, or environment

254
Q

What research complications can be caused by rat parvovirus?

A

Complications associated with tropism for mitotically active cells of fetuses, neonates, cell cultures, and tumors
Rat virus shown to modulate immune function through its tropism for T lymphocytes
Rat virus infx in diabetes-resistant BioBreeding rat increases expression of macrophage cytokines = autoimmune diabetes
Natural killer cell-mediated cytotoxicity increased in Brown Norway rats, decreased in Wistar-Furth rats
Effects of naturally occurring RPV, H-1, or RMV unknown

255
Q

What is the etiologic agent of rat theilovirus?

A

Rat theilovirus (RTV) - discovered in 2008 from feces of asymptomatic rat
Rats can seroconvert to Theiler’s murine encephalomyelitis virus (TMEV; genus Cardiovirus, species Theilovirus)
Other distinct rat cardioviruses - MHG virus, NSG910 virus

256
Q

What are clinical signs of rat theilovirus?

A

No clinical signs have been documented
RTV replicates in enterocytes of the small intestine and, following experimental inoculation, is shed for 4-8 weeks and does not leave the intestinal tract
Experimental intracranial inoculation with MHG caused paralysis in suckling rats, but this NOT replicated with RTV

257
Q

Describe the differential strain susceptibility of rat theilovirus.

A

Experimentally infx SD rats from one vendor exhibited prolonged fecal shedding and higher infectivity and seroconversion than SD rats from another vendor.
Immunodeficient nude rats exhibit persistent fecal shedding and the virus can be found in EXTRAINTESTINAL sites - suggest adaptive immunity is impt for elimination of the virus

258
Q

How is rat theilovirus diagnosed?

A

Serology, PCR - feces or intestine

259
Q

How is rat theilovirus controlled?

A

Little is known about control, but measures to control TMEV in mice should be effective
One report showed test and cull strategy was effective
Likely low to moderate presence in contemporary rat colonies based on serology survey

260
Q

What is the causative agent of pneumonia virus of mice?

A

Pneumonia virus of mice, genus Pneumovirus, species Murine pnuemonia virs (PVM), family Paramyxoviridae
Can infect mice, rats, hamsters, gerbils, G pigs, rabbits
Rare to non-existant in current rat colonies

261
Q

How is pneumonia virus of mice diagnosed?

A

Serology, PCR - trachea, lungs

262
Q

What is the pathology associated with pneumonia virus of mice?

A

Does not cause clinical disease
Multifocal, nonsuppurative vasculitis and interstitial pneumonititis with necrosis in acute phase of disease - lesions persist for several weeks
Historically considered a significant respiratory co-pathogen with Mycoplasma pulmonis, etc.
Cross species transmission a potential concern

263
Q

What is the causative agent of Group B Rotavirus infection?

A

Species Rotavirus B, genus Rotavirus, famile Reoviridae

264
Q

What are clinical signs of group B rotavirus?

A

Diarrhea in suckling rats (sometimes called infectious diarrhea of infant rats - IDIR), with erythema and bleeding or perianal skin
Same agent causes diarrhea in humans

265
Q

What pathology is associated with group B rotavirus?

A

Small intestinal villous atrophy, villous epithelial necrosis, syncytial cell formation

266
Q

How is group B rotavirus diagnosed?

A

Serology or PCR

Prevalence unknown but thought to be low

267
Q

Describe hantaviruses in rodents.

A

Enveloped RNA viruses; genus Hantavirus, family Bunyaviridae
Rodents are natural reservoirs, with each virus in the genus assoc w/ a specific rodent species
Infx in rodents is subclinical and virus is shed persistently in urine and feces

268
Q

Rattus norvegicus is the natural host for which hantavirus?

A

Seoul Hantavirus - causes hemorrhagic fever with renal syndrome (HFRS) in humans

269
Q

Cotton rats, Sigmodon hispidus, are reservoirs for which hantavirus?

A

A hantavirus that has induced Hantavirus pulmonary syndrome

270
Q

Describe ‘rat respiratory virus’.

A

The name given to a putative viral agent causing idiopathic histiocytic pneumonia in rats - now known these lesions are caused by PNEUMOCYSTIS CARINII infx

271
Q

List other viruses that can infect rats, but for which there is negligible data for clinical or pathological importance.

A

Mouse adenovirus, reovirus 3, parainfluenza virus 3, endogenous retroviruses

272
Q

Describe toxoplasmosis in rats.

A

Usually subclinical in rats, which are an intermediate host
Transmission to rats is via ingestion of cat feces; ingestion of infected intermediate hosts may also transmit infx
Rats can transmit T. gondii vertically, but only very poorly - in order for a rat colony to remain infected, cat feces would need to be repeatedly introduced
T. gondii is of little current significant in rat lab colonies

273
Q

Describe enteric flagellates seen in rat colonies.

A

Include order Trichmonadida (trichomonads) and genera Chilomastix and Hexamastix
Life cycle is direct with fecal-oral transmission
Trophozoites, the feeding form, are present in the GI tract
Reproduction is asexual and produces resistant cyst forms that are shed in the feces

274
Q

Describe Spironucleus muris.

A

Colonizes mice, rats, and hamsters
Inhabits glandular crypts and lumen of the small intestine
Age-infx relationships have been reported; rats and mice more susceptible under 6 weeks of age
Transmission between species (rats, mice, hamsters) appears to be poor

275
Q

How is Spironucleus muris diagnosed?

A

-Wet mounts of duodenal scrapings of weanling rats.
Phase contrast microscopy helpful to see trophozoites - 3-4x10-15 µm with rolling motion characterisitc of flagellated trophozoites
-Wet mounts or fecal smears to see cysts - 4-7 µm with characteristic banded pattern
-PCR - superior sensitivity

276
Q

Describe the environmental resistance of Spironucleus muris cysts.

A

Resistant to drying (room temp for 14 days), freezing (-20 C for 6 mths), pH 2.2 for 1 day, 0.1% glutaraldehyde for 1 hr

277
Q

Describe Giarda muris.

A

Colonizes wide range of mammalian hosts, incl rats, mice, hamsters
Trophozoites attach to surface of intestinal epithelial cells via a surface membrane mannose-binding lectin & can occur via any point on parasite surface
-Cysts in liquid feces have remained infective for at least 1 year
-Giardia spp. are ancient, have highly conserved genome, have own microbiome with mycoplasma-like particles and bacteria

278
Q

What are clinical signs of Giardia muris in rats?

A

No naturally occurring clinical disease in rats

-Experimental infx with G. lamblia and G. duodenalis results in secretion of specific immunoglobulin A into bile

279
Q

How is giardiasis diagnosed?

A

Feces or intestinal samples: Trophozoites - 7-13 x 5-10 µm, piriform or teardrop shape with a broad, rounded anterior tapering to a pointed posterior end; have slight curvature to ventral side so their multiple flagella cause a rolling motion; two darkly staining prominent nuclei & two darkly staining median bodies immediately posterior to the nuclei

  • Cysts may be seen in fecal smears or floats
  • PCR test with high sensitivity
280
Q

Describe Entamoeba muris.

A

Nonpathogenic, commensal amoeba of rats, mice, and hamsters

  • Trophozoites 8-30 µm in length found in wet mounts of cecum and colon contents, where they feed on bacteria
  • Cysts 9-20 µm diameter have 8 nuclei and can be found in feces
281
Q

What are control measures for intestinal flagellates and Entamoeba muris in rats?

A
  • Rederivation by C-section or embryo transfer
  • Clean contaminated rooms with chlorine dioxide or other suitable disinfectant prior to repopulating
  • All materials brought into room that may have previous rodent/rodent feces contact should be autoclaved
  • Monitor animals at 3-6 weeks of age for infection prior to introduction
282
Q

How are intestinal flagellates in rats treated?

A

Limited success in treating

  • Metronidazole or dimetridazole can be added to drinking water BUT is ineffective for cysts in the environment
  • Metronidazole has been shown to be CARCINOGENIC in mice and rats
283
Q

Describe Syphacia muris in rats.

A

Most common oxyurid of rats

  • Slightly smaller than S. obvelata and male has a longer tail measured in proportion of body width
  • Eggs 72-82 x 25-36 µm; slightly flattened on one side
  • Direct life cycle of 11-15 days; transmission horizontal via ingestion of eggs
  • Eggs remain viable at room temp for weeks to months; deposited around anus and in colon and infective in ~6 hr –> ingested during grooming, hatch in small intestine, larvae mature in cecum in 10-11 days
  • Diagnosis: perianal tape test for eggs, direct exam of large bowel, PCR; screening for eggs SIG less sensitive than looking for adults in GI; best is multiple tests
  • Transmission to sentinel animals may be delayed - test colony animals
284
Q

Describe Syphacia obvelata in rats.

A

More frequently found in mice, hamsters, gerbils; occasionally in rats esp when housed in same room as infested mice

  • Eggs LARGER than S. muris - 118-153 x 33-55 µm; eggs are almost completely flat on one side
  • Direct life cycle of 11-15 days; transmission horizontal via ingestion of eggs
  • Eggs remain viable at room temp for weeks to months; deposited around anus and in colon and infective in ~6 hr –> ingested during grooming, hatch in small intestine, larvae mature in cecum in 10-11 days
  • Diagnosis: perianal tape test for eggs, direct exam of large bowel, PCR; screening for eggs SIG less sensitive than looking for adults in GI; best is multiple tests
  • Transmission to sentinel animals may be delayed - test colony animals
285
Q

Describe Aspiculuris tetraptera in rats.

A
  • Recognized by 4 cervical alae on anterior end of body
  • Eggs similar size to S. muris - 89-93 x 36-42 µm, bilaterally symmetrical
  • Horizontal transmission by ingestion of eggs; eggs extremely persistent in environment
  • LONGER life cycle than Syphacia of 23-25 days
  • Eggs passed in feces
  • Diagnosis: Fecal float or fecal concentratio and centrifugation; examine cecum and colon; PCR; multiple tests is best
  • Transmission to sentinels may be delayed
286
Q

Describe prevention and control of Syphacia and Aspiculuris in rats.

A
  • Fenbendazole (ovacidal, larvacidal, adulticidal), ivermectin (NOT ovicidal; cab have deleterious effects), new generation avermectins, levamisole can all be effective tx
  • Topical selamectin & moxidectin in diet = INEFFECTIVE
  • Environmental decontamination: heat, ethylene oxide, formaldehyde gas, chlorine dioxide with or without didecyl di-methyl ammonium chloride
  • Potassium peroxysulphate, alcohol, chlorhexidine, UV light = INEFFECTIVE
  • Rederivation and following barrier room practices
287
Q

What are research complications of oxyuriasis in rats?

A

Can interfere with adjuvant arthritis, growth rate, intestinal electrolyte transport, cardiac reactivity to b-adrenergic stimulation, and the immune response to allergic sensitization

288
Q

Describe Trichosomoides crassicauda.

A

Trichurid nematode found only in the rat; geographically widespread but virtually nonexistent in rederived rats
-Adult females, ~10 mm long, live in the urinary bladder lumen or embedded in the mucosa; males are anatomically degenerate and exist symbiotically in the vagina or uterus of the females

289
Q

What are clinical signs of Trichosomoides crassicauda?

A

Usually clinically inapparent

  • Usually very few worms in bladder & cause mild uroepithelial hyperplasia
  • Worms in renal pelvis assoc. w/ pyelitis and pyelonephritis
290
Q

Describe the life cycle of Trichosomoides crassicauda.

A

Embryonated eggs laid and passed in urine - transmission is ingestion of these eggs, probably from dams to pups - eggs hatch in stomach, penetrate wall and pass through peritoneal cavity/bloodstream to lungs and other organs - may cause hemorrhage or granulomas where lodge in tissues - ONLY larvae that reach bladder or kidney develop to maturity
Entire life cycle = 8-9 weeks; eggs not present in urine until rats 8-12 weeks old

291
Q

Describe the pathology of Trichosomoides crassicauda infection.

A

Early study thought assoc. w/ bladder tumors in rats fed high doses of saccharin in diet = NOT supported by further investigation
Proliferative changes in urothelium - identical to those in early carcinogenesis by chemical compounds like N-methylnitrosurea (MNU)

292
Q

How is Trichosomoides crassicauda diagnosed?

A
  • Filter urine and examine for eggs
  • Direct examination of bladder wall, histopath, electron microscopy, microscopic examination of CRYOSTAT section with ACRIDINE ORANGE
293
Q

What is the treatment for Trichosomoides crassicauda in rats?

A

Ivermectin - single dose usually effective

294
Q

What are research complications of Trichosomoides crassicauda in rats?

A

None reported; but proliferative changes to urothelium would render these animals unsuitable for research on urinary system

295
Q

Describe Rodentolepis nana (Hymenolepis nana).

A

Direct life cycle, zoonotic; 20-40 mm long but can vary greatly, slender, less than 1 mm wide
Scolex has 4 suckers & rostellum armed with 20-27 hooks
Mature proglottids are trapezoidal, contain up to 200 eggs - thin-shelled, oval, colorless, have six visible polar filaments; within the eggs, the embryo (oncosphere) has three pairs of hooklets within an inner envelope
Eggs ~30-56 x 44-62 µm, do not persist for long outside host

296
Q

Describe Hymenolepis diminuta.

A

Indirect life cycle with an intermediate host, NOT zoonotic
Larger than R. nana - 20-60 mm long and 3-4 mm wide
Scolex has 4 suckers, rostellum has NO HOOKS
Eggs are 60-88 x 52-81 µm; oncosphere has three pairs of hooks but NO polar filaments

297
Q

Describe Taenia taeniaformis (Cysticercus fasciolaris).

A

Cysts are found in livers of rats, mice, hamsters & up to several cm in diameter
Cysts includes scolex, strobila, and bladder
Considered nonpathogenic but may be assoc. w/ development of hepatic sarcomas (prob. similar mechanism as sarcomas in rats d/t foreign bodies)
Definitive host is the cat - presence in rat colony indicates that something in environments, usually feed, contaminated with unsterilized cat feces.

298
Q

Describe life cycle of Rodentolepis nana.

A

Lives in small intestine of rats, mice, hamsters, & primates (incl humans); causes little damage to rats or mice, main concern is that ZOONOTIC
Not clear if strains in rats are infective to humans
Direct life cycle of 14-16 days: embryonated eggs are ingested and hatch in small intestine - oncospheres penetrate villi and develop into cysticercoid larvae in 4-5 days - larvae reenter the lumen, scolex evaginates, attach to mucosa - mature proglottids formed in 10-12 days
Adults only live a few weeks; infx normally results in some level of immunity that presents autoinfection - when autoinfection occurs, eggs hatch and develop in small intestine without passage in feces = can cause very high worm burdens
Indirect life cycle: grain beetles (Tenebrio molitor & Tenebrio obscurus) & fleas (Pulex irritans, Ctenocephalus canis, Xenopsylla cheopis) serve as intermediate hosts - rats eat these intermediate hosts

299
Q

Describe life cycle of Hymenolepis diminuta

A

Host range of mice, rats, hamsters, and primates (incl humans)
ALWAYS INDIRECT life cycle: grain beetles (Tenebrio molitor & Tenebrio obscurus) & fleas (Pulex irritans, Ctenocephalus canis, Xenopsylla cheopis) serve as intermediate hosts - rats eat these intermediate hosts

300
Q

What are clinical signs of Rodentolepis nana and Hymenolepis diminuta in rats?

A

Pathogenic only when severe infection - retarded growth, weight loss, impaction, death.
NO associated pathologic lesions

301
Q

How are Rodentolepis nana and Hymenolepis diminuta diagnosed and controlled?

A

Dx: adult cestodes on direct exam of small intestine; eggs in fecal smear or float; histopath detection of cysticercoids or adults in small intestine
Infx most common in recently weaned and young adults, prob b/c acquired immunity in older animals
Prevent: purchase clean stocks of rodents; adequate disinfection of barrier room supplies; insect control and exclusion of wild rodents
Tx: NOT generally recommended d/t zoonoti concerns

302
Q

What are potential research complications of Rodentolepis nana and Hymenolepis diminuta?

A

Experimental H. diminuta infx has elicited a Th2 type immune response that may modulate models of intestinal and extraintestinal disease

303
Q

What trematodes have been reported in wild rats?

A

Plagiorchis muris, Plagiorchis philippinensis, Plagiorchus javensis
Some are zoonotic, but none are significant in laboratory rats.

304
Q

Which species of fur mites may be seen in laboratory rats?

A

Radfordia ensifera - most likely

Radfordia affinis, Myobia musculi

305
Q

How are fur mites transmitted?

A

Transmitted by eggs, which can persist in environment for long periods
Eggs hatch after 7-8 days & females can begin to lay eggs after another 16 days

306
Q

What are clinical signs of fur mites in rats?

A

Pruritis, self-excoriation, secondary bacterial infx

307
Q

How are fur mites in rats diagnosed?

A

Similar to mice
Fur pluck, tape test, skin scrape, examination of cool rat or pelt under dissecting microscope, PCR
Detection using indirect sentinel monitoring has mixed success in mice

308
Q

What are treatment options for fur mites in rats?

A

Treatments developed in mice likely applicable to rats
Topical selamectin alone or in combo with amitraz- or fipronil-treated nestlets; topical moxidectin; ivermectin topically or in feed or water with or without cross fostering
-Ivermectin has been assoc. w/ neurologic signs in mice
-Can also eliminate with rederivation and proper adherence to barrier room practices

309
Q

What are potential research complications of fur mites?

A

In mice, fur mite infestation has been assoc. w/ increased mitotic activity in the skin, immunologic alterations, amyloidosis, and a Th2 immune response that results in elevation of serum IgE

310
Q

What species of blood-sucking mites can infest rats?

A

Ornithonyssus bacoti (tropical rat mite) & Laelaps echidnina
Blood-sucking mites, only found on rat while feeding
Clinical signs: range from none to anemia & debility with severe infestations
These mites carry several rodent pathogens & will also bite humans and carry zoonotic agents
Diagnosis: direct observation of blood-engorged mites on rats, in environment, on sticky tape traps
Treatment: Permethrin-impregnated cotton balls ofr mice and pyrethrin permethrin or dichlorvos treatment of the environment

311
Q

Describe Polyplax spinulosa

A

Only cause of pediculosis seen in laboratory rats; rare
Females 0.6-1.5 mm long, females larger than males; all have 6 legs
Females lay eggs that are cemented to hairs - eggs have distinct operculum, with a row of pores near the operculated end - eggs hatch by pneumatic mechanism in 5-6 days (larvae ingest air through the pores, pass it through the body, and use that to expel that operculum - young nymphs are paler than yellow-brown adults but morphologically similar - after 3 ecdyses (molts) become adults; depending on environment ecdyses take 1-3 weeks
Entire life cycle 2-5 weeks; adults live 25-28 days; transmission by direct contact
Vector of Mycoplasma haemomuris & other pathogens

312
Q

What are clinical signs of pediculosis in rats?

A

Heavily parasitized animals may be pruritic, unthrifty

313
Q

How is Polyplax spinulosa infestation diagnosed?

A

Direct exam of pelt for adults, nymphs, eggs

Any time P. spinulosa is detected, blood smears should be screened for Haemobartonella muris

314
Q

How is Polyplax spinulosa prevented/controlled?

A

Insecticides approved for veterinary use and SC ivermectin may be effective for treatment.
Prevention is by only introducing animals free of lice

315
Q

Describe Pneumocystis carinii.

A

Classified as a fungus based on DNA base sequences in genes encoding ribosomal RNAs
Causes two distinct diseases in immunocompetent vs. immunodeficient rats
Airborne transmission & possibly fomites like soiled bedding

316
Q

What is the disease presentation of Pneumocystis carinii in immunodeficient rats?

A

Proliferates uncontrolled in the lung, filling alveoli & causing dyspnea, wasting, death
-Foamy material comprising trophozoites, phospholipids, macrophages, and debris filling alveoli; infx in nude rats also had interstitial and perivascular infiltration
Dx: methamine silver stain - demonstrates fungal cysts in alveoli and bronchioles
Rats with induced immunocompromise also infx w/ P. carinii to model P. jirovecii pneumonitis in humans with HIV

317
Q

What is the disease presentation of Pneumocystis carinii in immunocompetent rats?

A

Interstitial pneumonia - previously called “Rat Respiratory Virus (RRV)”; lesions occur following infx regardless of rat age
P. carinii has a slow doubling time of 4.5 days & does not incite a host response until a population density threshold is reached - then lesions begin to be visible and specifics Abs are produced - then P. carinii diminishes and infex is eventually cleared
Low population density in immunocompetent rats may make P. carinii difficult to detect

318
Q

What pathologic lesions are associated with P. carinii?

A

Gross lesions become visible in 50% of more of infected rats 4-5 wks after infx

  • Red-brown or tan lesions throughout lungs in interstitial pattern - lymphohistiocytic interstitial pneumonia; lesions may be resolved in another 8-12 wks
  • Immunocompetent rats: alveolar septae thickened w/ macrophages & lymphocytes, alveoli contain macrophages, lymphocytes, debris; multinucleated giant cells occasionally; slight interstitial hemorrhage common; perivascular lymphocyte cuffing - bands of macrophages & lymphocytes encircle interstitial arteries - over time lymphocytes predominate & lymphoid cuffs persist after alveolar and septal infiltrates have resolved
319
Q

How is P. carinii diagnosed in rats?

A

Characteristic histo lesions, PCR of lung tissue (best) or PCR of bronchial wash or nasal swabs (oral swabs INeffective); methamine silver stain to demonstrate fungal cysts in alveoli
Screening rat groups by serology or PCR; rats produce Abs 6-8 wks after infx and remain Ab positive for life

320
Q

What are differential diagnoses for P. carinii in rats?

A

Characteristic lymphohistiocytic interstitial pneumonia must be differentiated from the bronchial or bronchiolar inflammation of Mycoplasma pulmonis, CAR bacillus, Sendai virus, coronavirus

321
Q

What are research complications of P. carinii in rats?

A

Confounding factor for inhalation studies; may impact pulmonary or cardiopulmonary studies.

322
Q

Describe Encephalitozoon cuniculi.

A

Microsporidian fungal parasite; wide variety of mammal hosts - rodents, lagomorphs, carnivores, primates (incl humans) & birds
Resistance to infx and outcome of infx dependent on T-cell function, which is strain-dependent (athymic nude mice, and presumably athymic nude rats, are more susceptible)

323
Q

How is Encephalitozoon cuniculi transmitted?

A

Ingestion, possibly inhalation, of spores shed in urine

Vertical transmission proposed in primates, foxes, mice, rabbits, guinea pigs, but not rats

324
Q

What are clinical signs of Encephalitozoon cuniculi in rats?

A

No clinical signs reported in rats.

325
Q

Describe pathology of Encephalitozoon cuniculi in rats.

A

Nonsuppurative or granulomatous meningioencephalitis in any or all parts of brain & occasionally spinal cord, less frequently similar lesions in other tissues
Spores may be observed in or adjacent to lesions - strongly GRAM (+), stain poorly with H&E

326
Q

How is E. cuniculi diagnosed?

A

Serology - positives should be confirmed by a second method or repeating the assay
Histopath or PCR - kidney, urine, bladder preferred sampling sites

327
Q

What are differential diagnoses for E. cuniculi?

A

E. cuniculi - 1x2 µm, stains well with Gram stain but poorly with H&E
Toxoplasma gondii - 2x4 µm, stains well with H&E but poorly with Gram stain

328
Q

What are recommended control measures for E. cuniculi?

A

Only purchase animals free of E. cuniculi

Currently NO effective treatment

329
Q

What are potential research complications of E. cuniculi?

A

Research complications have not been reported in rats, but could confound studies with histopath exam of kidneys or CNS

330
Q

Describe Aspergillus fumigatus infection in rats.

A

Reported in Wister rats; predisposing factor thought to be Sendai virus
-Clinical signs: snuffling, nasal exudate
-Pathology: yellowish, friable material in nasal cavities, ; in most cases A. fumigatus-induced rhinitis limited to the naso- and maxilloturbinates; one rat had a bronchial abscess
Trachobronchial aspergillosis reported in an aged F-344 rat w/ immunodeficiency d/t leukemia thought to be involved - necrotic lesions of trachea and bronchi
Another case study of fungal rhinitis in rats without immunosuppression suggested that autoclaved or gamma-irradiated bedding should be used to eliminate possible fungi in bedding

331
Q

Describe Trichophyton mentagrophytes in rats.

A

Has not been reported in lab rats in many years

In rats dermatomycosis presents with patchy hair loss, scruffy, erythematous papular-pustular lesions

332
Q

Eosinophilic granulomatous inflammation

A

Brown Norway rats have high incidence, nearing 100% in males and females at 3-4 months old

  • Rats of other strains maintained with Brown Norway do not develop lesions
  • Lung lesions scattered through parenchyma; well-organized granulomas of Langhans’ giant cells, macrophages, eosinophils
  • Brown Norway used for studies of allergy & asthma due to inherent pulmonary hyperresponsiveness
  • May be result of an allergic or reactive response to environmental insult
333
Q

Polyarteritis nodosa

A

Sprague-Dawley & spontaneously hypertensive rats
Vascular disease; gross lesions in large, muscular arteries of the mesentery and visceral organs that become enlarged and tortuous
-Histo of affected arteries: fibrinoid necrosis, muscular hypertrophy
-Rupture of affected arteries potential cause of sporadic death

334
Q

Heat and moisture, such as with autoclaving, and prolonged storage can impact levels of what nutrients in rodent diets?

A

Lysine, Vitamin A, Vitamin E, Riboflavin, Thiamin

335
Q

Describe clinical signs of vitamin deficiencies in rats.

A

Decreased reproductive performance, litter loss, poor growth, sparse hair coat
Hypovitaminosis A: squamous metaplasia of salivary ducts
Hypovitaminosis K: disseminated hemorrhage
Hypovitaminosis E: embryonic death and testicular degeneration

336
Q

Describe ringtail.

A

Associated with relative humidity <40%
Primarily in young rats, usually sucklings
Prominent annular constrictions of tail and occasionally digits; areas distal to constrictions can become ncrotic and slough
-Normal, more subtle tail annulations develop as rats age

337
Q

Describe disorders in rats associated with light exposure.

A

Retinal degeneration can occur with as little as 270 lux irradiation at cage level on a 12:12 light cycle.
1600 lux (very high light) for 12 hrs a day for 8 days resulted in Harderian gland necrosis - photoreactive properties of porphyrin secretions
Historic light recommendations of 325-400 lux at 1 m above floor - may NOT accurately tell cage level light exposure
-Light energy exposure = distance-squared function
-Light exposure as low as 0.21 lux during dark cycle can disrupt metabolic and tumor studies

338
Q

Describe ulcerative dermatitis in rats.

A

Associated with S. aureus and self-induced trauma from scratching.
-May be related to specific Staphylococcus phage types or host susceptibility factors

339
Q

Adynamic ileus

A

Associated with IP choral hydrate.
Pathology can be mistaken for Tyzzer’s disease
Clin signs: several days after anesthesia see lethargy, anorexia, abdominal distension - prominent dilation of jejunum, ileum, cecum
CONCENTRATION, not dose, of chloral hydrate appears correlated with induction of ileus

340
Q

At what age do most neoplasms occur in rats?

A

Greater than 18 months old, other than mammary gland fibroadenomas in many stocks and testicular tumors in F-344 rats

341
Q

How can diet modulate tumor prevalence in rats?

A

Dietary factors include manipulation of dietary composition - high fat, specific amino acid deficiencies, high protein levels, caloric intake

  • High protein may alter chronic progressive nephropathy (CPN) which can, in turn, alter development of renal neoplasia
  • Rats fed ad lib have lower survival and more tumors, esp pancreatic, mammary, and pituitary where endocrine influences play a role
342
Q

What is the effect of disease status in rats on tumor prevalence?

A

Some infectious diseases can affect longevity, pre-neoplastic or neoplastic changes, and mask small tumors

343
Q

Describe mammary tumors in rats.

A

Most frequently occurring tumors in most stocks and strains of rats.
50% incidence in aged SD, 25-30% F-344, 30% or less Wister Han; both types can occur in aged males but incidence usually less than 1%
Most common = benign fibroadenomas; carcinomas less common
BENIGN FIBROADENOMAS: freely moveable in SC, circumscribed, firm, lobulated; on histo characterized by well-differentiated acinar epithelial components surrounded by inter- and intralobular connective tissue components

344
Q

Describe testicular tumors in rats.

A

INTERSTITIAL CELL TUMORS: 80% F-344 by 15 months, much less common in SD & Wistar Han

  • Discrete, soft, yellow to brown with areas of hemorrhage, may occur at multiple sites unilaterally or bilaterally
  • Histo: Leydig cell origin; two cell types arranged in solid sheets or in an organoid pattern - 1) polyhedral to elongated cells with granular to vacuolated cytoplasm, 2) smaller cells with hyperchromatic nuclei and scant cytoplasm
345
Q

Describe pituitary tumors in rats.

A

Frequent in SD, F-344, and Wistar Han

  • Most common = CHROMOPHOBE ADENOMAS, originating from PARS DISTALIS; carcinomas of pars distalis much less common
  • Caloric restriction significantly reduces incidence of pituitary tumors in rats
  • Chromophobe Adenomas: soft, dark red d/t prominent hemorrhagic areas; well circumscribed, press against adjacent brain and cause hydrocephalus; histo: large polygonal cells with prominent vesicular nuclei and eosinophilic cytoplasm; cells arranged in nests, cords, or sheets separated by vascular sinusoids
346
Q

Describe adrenal tumors in rats.

A

Cortical adenoma: SD 2% males, 5% females; low incidence in F-344
Pheochromocytoma: ~85% benign; SD 14% males, 2% females; F-344 32% males, 5% females

347
Q

Describe pancreatic tumors in rats.

A

Pancreatic islet cell endocrine adenomas & carcinomas; single or multiple, circumscribed and reddish brown

  • SD 8% males, 3% females; Wistar Han low incidence males and females; F-344 4% males, 1.5% females
  • Carcinomas distinguished from adenomas by capsular invasion and metastases
  • Tumors of exocrine pancreas less common
348
Q

Describe tumors of lymphoreticular system in rats.

A

LARGE GRANULAR LYMPHOCYTIC LEUKEMIA: F-344 34% males, 20% females; SD & other strains incidence quite low; initial site of malignancy thought to be spleen; unlike in mice, NOT assoc w/ retrovirus
-Diagnosis: anemia, jaundice, weight loss, splenomegaly, elevated leukocyte counts of up to 400,000/mL, diffue infiltration of malignant lymphocytes in various organs
LYMPHOCYTIC LYMPHOMA & HISTIOCYTIC SARCOMA: each incidence of <1% in SD & Wistar Han

349
Q

Hydronephrosis in rats

A

Common congenital defect in rats; unilateral or bilateral dilation of the renal pelvis

  • May be inherited as a single dominant gene in the Gunn rat; appear to be polygenic in Brown Norway and SD
  • Right kidney affected more than left; ureter may also be affected
  • Normal renal pelvis of young animals may appear dilated, so caution in interpreting
  • Ddx: pyelonephritis (material in pelvis typically cloudy), polycystic kidney disease, renal papillary necrosis; culture and histopath will distinguish condition
350
Q

Describe congenital cardiovascular defects in rats.

A

Ventricular and atrial septal defects, dextrocardia, defects of valves and endocardial cushion, anomalies of great vessels

  • One colony of SD had 2.3% incidence of cardiac defects
  • Wistar-Kyoto inbred rat, used as control for outbred spontaneous hypertensive rat (SHR), has high rates of cardiac septal defects resulting in right ventricular hypertrophy
351
Q

Which rat strain is particularly susceptible to seizures?

A

Wistar rats. Used in investigation of audiogenic seizures

352
Q

Describe ocular defects in rats.

A

Retinal degeneration: age-related lesion, can be accelerated by light exposure; in albino rats lack of pigmented tapetum increases light exposure to retina and predisposes for retinal atrophy
Corneal mineralization: 10-100% incidence in F-344; deposition of calcium salts, often visible in stained sections as basophilic granules, along the interface of corneal epithelium and stroma
Cataracts, osseous and cartilaginous metaplasia of the sclera, colobomas

353
Q

Transverse vaginal septum in rats.

A

Female Wistar and SD rats; affected animals functionally sterile is septum is complete, subfertile if partial

354
Q

Pseudohermaphroditism in rats.

A

Also known as testicular feminization
Testes present internally but external genitalia approximately female
Affected rats are XY but express default female phenotype
Testicular-feminized rat (tfm) = defect d/t lack of androgen receptors due to a point mutation

355
Q

Chronic progressive nephropathy (CPN) in rats.

A
  • More common in males
  • Gross lesions first observed in rats more than 6 months old w/ pitting of cortical surface; b/c of cortical interstitial fibrosis, removal of the renal capsule may tear the cortical parenchyma; cortical surface becomes increasingly irregular with time and may develop areas of pallor
  • Histo: thickened basement membranes, thickening of capillary tufts, adhesions to the parietal layer of Bowman’s membrane, segmental glomerulosclerosis; numerous tubules in both the cortex and medulla become dilated and filled w/ eosinophilic proteinaceous casts
  • Secondary hyperparathyroidism can occur subsequent to renal compromise & widespread dystrophic mineralization
356
Q

What is the etiology of chronic progressive nephropathy in rats?

A

Unknown, likely multiple factors

  • Varies with strain so probably some genetic predisposition; SD & F-344 have high incidences whereas Wistar and Long-Evans have lower incidence
  • Gender: males have earlier onset, higher incidence, greater lesion severity than females
  • Diet: moderate dietary restriction (25-30% reduction in caloric intake) greatly reduces incidence and severity; hypothesis is that overfeeding results in prolonged increases in renal blood flow and glomerular filtration rate - hyperfiltration causes glomerular hypertrophy, leading to macromolecule filtration deficits, mesangial damage, glomerulosclerosis, and protein leakage
357
Q

Nephrocalcinosis in rats.

A

Deposition of calcium phosphate in renal tissue

  • More common in females; incidence varies with age and strain; may occur in in F-344 rats as young as 7 weeks old; up to 50% incidence in F-344, 0-7% in SD and Wistar; very high incidence in BDIX rats
  • Incidence and severity may be increased by dietary manipulations including high levels of calcium, high phosphorus, low calcium/phosphorus ratios, low magnesium
  • Histo: mineral deposition observed most frequently at the corticomedullary junction, in cells of the pars recta and thin loops of Henle as well as in lumen of these tubules
358
Q

Urolithiasis in rats.

A

Formation of mineral deposits within the urine, occasionally observed in the renal pelvis and/or urinary bladder

  • Incidence generally low; sporadicallyobserved in aging rats of both sexes; detection in rats less than 6 months indicated bacterial infx - ascending E. coli
  • Copulatory plugs occasionally found in bladders and urethras of male rats and can be mistaken for uroliths
  • Rats predisposed to urinary tract infx include Zuckrer Diabetic Fatty rat, rats with hydronephrosis
  • Uroliths usually calcium phosphate and struvite
359
Q

Cardiomyopathy in rats.

A

Major cause of death in aged male rats of multiple strains, including SD, when fed ad lib

  • Heart is enlarged, occasionally with pale streaks visible; increased weight of heart correlates well with the degree of damage observed on histo
  • Histo: necrosis of myocardial fibers, interstitial infiltration of mononuclear cells; later in course of disease fibrosis becomes more prominent; large reactive nuclei in myofibers
  • Most commonly affected myocardial sites are the papillary muscles and interventricular septum
  • Incidence can be dramatically reduced at any age by moderate restriction of caloric intake by 25-30%
360
Q

Skin and hair changes with age in rats.

A
  • Thinning or loss of hair, especially over the back; common in Brown Norway rats
  • Albino rats have more yellow appearance over time due to accumulation of sebum in the skin
  • Rings of scales covering the tail increase in number to 190 at 1 year; become more prominent and yellow with time; yellowish material on the tail and adjacent to the ear may become black with time probably d/t oxidation and/or bacterial action
  • Males accumulate brown-pigmented foci on the skin termed scales; scales can be detached and overlay skin of ‘normal’ color; on dorsum, tail, and perineum; nature of pigment is unclear, may be oxidized lipid or amino acids
361
Q

Alveolar histiocytosis in rats.

A

Very common incidental finding in the lung of aging rats of many stocks and strains

  • Grossly, white to pale tan foci, usu ~1mm in diameter, visible on the pleural surface; foci may extend slightly above the pleural surface in uninflated lung
  • Histo: clusters of alveoli, often in subpleural locations or adjacent to a terminal bronchiole, contain increased numbers of large, pale, foamy-appearing macrophages; cholesterol clefts may be visible in dense macrophage aggregates; slight infiltration of lymphocytes may be present around adjacent vessels - response to proinflammatory mediators released by the macrophages
  • Cause unknown; not considered infectious