Chapter 5. Biology and Diseases of Hamsters Flashcards
What is the scientific classification of hamsters?
Order Rodentia, Suborder Myomorpha, Superfamily Muroidea, Family Cricetidae
Animals in this family characterized by large cheek pouches, thick bodies, short tails, excess of loose skin
What is the dental formula of hamsters?
(I 1/1, C 0/0, PM 0/0, M 3/3) x 2 = 16
Incisors erupt continuously
Cuspidate molars that do NOT continue to grow
Describe the Syrian or golden hamster (Mesocricetus auratus).
Originated in Syria and naturally lives in arid, temperature regions of southeast Europe and Asia Minor
Lives in deep tunnels that provide cooler temps and high humidity
Nocturnal in the laboratory, but females may be diurnal in wild
Adult Syrian hamster: 6-8 inches (14-19 cm); 110-140 gram weight; females tend to be larger than males
Males can be identified by prominent flak glands and by large testicles that protrude on either side of tail
Who initiated the use of the golden hamster in research?
Saul Adler. Looking for a laboratory animal susceptible in infection with Leishmania
Almost all Syrian hamsters in laboratories originated from one litter captured in Syria in 1930; 3 littermates retained in captivity and their progeny first imported in US in 1938; lab use of hamsters grew to a peak in early 1970s and then declined
What cancers are golden hamsters used to study?
Oral tumors - cheek-pouch carcinogenesis model
Pancreatic ductal adenocarcinoma - administered nitrosamines or a transplantable cell line
Respiratory tract tumors - administered carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to w/ or w/out hypoxia to develop nonsmall cell lung carcinoma
Disease process of Simian virus 40 (SV40), a polyomavirus - hamsters develop variety of tumors based on route of inoculation and age of hamster
Effect of exogenous estrogen compounds on tumor development - 100% male hamsters developed renal tumors in one study when administered estrogens
Hamsters are one of few animal models that permit the replication of human adenoviruses
What metabolic syndromes are golden hamsters used to study?
Cholesterol cholelithiasis - induced via excess dietary cholesterol or sucrose-rich diet
Diabetes mellitus - induce with streptozotocin (STZ) or alloxan; giving nicotinamide IP 15 min before STZ results in partial protection against betacytotoxic effect of STZ and partial presevation of insulin stores; also induce with high fat, modest cholesterol diet - induce diabetes in 2 wks w comorbidities like obesity, hyperinsulinemia, hyperleptinemia, hypercholesterolemia, hypertriglyceridemia
Diabetes with nephropathy and coronary lesions - Syrian hamsters of albino-panda-albino (APA) strain when injected with STZ
Atherosclerosis - Syrian hamsters possess similar lipid metabolism to humans; induced via diet
What cardiovascular diseases are golden hamsters used to study?
Cardiomyopathy - naturally occurring in Syrian hamsters, inherited, model for both hypertrophic and dilated cardiomyopathies; both DCM & HCM in hamsters caused by defect in sarcoglycan gene, a component of the dystrophin complex
Cardiomyopathic hamster lines - original polymyopathic line 1.50, BIO 82.62, BIO TO-2, BIO 53, UMX-7.1
Some strains characterized by significant cardiac hypertrophy, some by ventricular dilation without hypertrophy, some compensatory hypertrophy progressing to left ventricular dilation
What infectious diseases are golden hamsters used to study?
Hantavirus pulmonary syndrome
Coronavirus severe acute respiratory syndrome (SARS)
Fungal infections incl Histoplasma spp. - sensitive to small inocula; most fungi grow in spleen, liver, and LNs
Mycoplasma pneumoniae - models of localized infx in respiratory tract
Mycobacteria spp., Clostridium difficile, Treponema pallidum, Toxoplasma spp., Babesia spp., leprosy, atypical TB, leptospirosis
Prions - susceptible to scrapie - prions replicate to high titers in brains of hamsters, transmissible mink encephalopathy (TME), Creutzfeldt-Jakob disease, Gerstmann-Staussler syndrome (GSS) - cause slow progressive degenerative diseases in the CNS; Hamsters develop amyloid-like deposits in their brains that may be similar to amyloid in human Alzheimer’s
What other various diseases are golden hamsters used to study?
Chronic obstructive pulmonary disease (COPD) & emphysema - induce w/ single intratracheal dose of porcine pancreatic elastase or a copper deficient diet
Gastropathy due to NSAIDs
Assessment of human fertility - hamster oocyte penetrable to human spermatozoa = zona-free hamster oocyte assay - analyzes ability of sperm to capacitate eggs, undergo acrosome reaction, and fuse with oocyte; becoming less popular with development of new techniques like intracytoplasmic sperm injection
What are neonatal developmental milestones for hamsters?
Incisors are visible at birth; weight 2-3 g at birth
Ears open at 4-5 days, hair growth first noted day 9, eyes open at 14-16 days
Weaned at 21 days & weigh 35-40 g
Maturity at 6-8 weeks - males weigh 85-110 g and females 95-120 g
What is the reproductive life span for hamsters?
Begins at 6-8 weeks & continues until 14 months old
What is the life span of hamsters?
Average 2 years (18-24 months), up to 3 years.
Average female life span may be markedly shorter than males, depending on strain and source
When is the optimal time in gestation of hamsters for teratogenic studies?
Day 8 of pregnancy - hourly development of the fetus can be observed
Describe the cheek pouches of hamsters.
Non-glandular, contain lots of mast cells, highly vascular, lined with stratified squamous epithelium.
Blood supply comes from branches of external carotid artery - supplied by 6 small arteries in the neck and face
Pouches can be easily everted - used to study microvascular studies of inflammation, tumor growth, vascular smooth muscle function, ischemia reperfusion
“Immunologically privileged” b/c lack intact lymphatic drainage - surface density of Langerhans cells markedly decreased in pouches - will support growth of foreign tissue without immunological rejection
What influences development of caries in hamsters?
Retention of fine food particles between crown teeth, amount of carbohydrate in diet, form of carbohydrate in diet, vitamins (+/-) in diet; possibly infectious bacteria transmissible between rodents orally
Describe the stomach of hamsters.
Glandular stomach and nonglandular forestomach, separated by the incisurae of the greater and lesser curvatures.
Nongladular forestomach similar to ruminant stomach, with elevated pH and microflora that contribute to digestion through fermentation
What neoplasias can occur in the GI tract of hamsters?
Depends on age, strain differences, breeding environment, diet, and other unknown factors.
Two studies showed high incidence of spontaneous neoplasms in the GI tract, others did not confirm.
Experimental induction of papillomas, adenocarcinoma in forestomach and intestines, adeomatous polyps in the colon
How do Syrian hamsters respond to intragastric administration of purified cholera enterotoxin?
Intraluminal accumulation of fluid in small bowel, cecum, proximal colon.
Historical model to study pharmacological agents, like indomethacin, polymyxin B sulfate, glucose electrolyte solutions, and colchicine that may inhibit intestinal fluid secretions
Describe the pancreas and gallbladder of hamsters.
Major pancreatic ducts join the common bile duct shortly before it enters the duodenum.
Anatomical configuration is similar to that of mice and rats, but distinct from other mammals including humans.
Syrian hamster can serve as model for pancreatic carcinogenesis - most commonly induced by SC nitrosamines; transplantable cell line (PGHAM-1) can also reproduce metastatic pancreatic cancer
Describe the pulmonary system of the Syrian hamster.
Conductive airways contain a limited number of glandular structures, primarily in the proximal trachea, which facilitates modeling chronic bronchitis.
Pulmonary vascular bed is similar to that of humans; hamsters develop pulmonary lesions that resemble human centrilobular emphysema when given intratracheal porcine pancreatic elastase
Spontaneous bronchiogenic and pulmonary cancers are rare = Syrian hamsters are good model to study chemical carcinogenesis in resp tract
Why is the Syrian hamster kidney highly responsive to estrogen?
Their reproductive and urogenital tracts develop from the same embryonic germinal ridge.
Administration of estrogen to males leads to renal tumors - model of effects of exogenous estrogenic compounds on tumor development
Hamsters one of most reliable models for effect of chemical carcinogens on the urinary bladder
Describe endocrine system of hamsters.
First model reported with equivalent of Addisonian adrenal necrosis.
Adrenals show distinct size difference by 4 weeks of age, depending on sex - males have greater number of reticular cells within the adrenal cortex = double size adrenals compared to females
Why do hamsters not reject skin allografts to same extent as other laboratory animal species?
Littermates have very little alloantigenic variation & few mutational changes have occurred in their defined gene pool While there is diversity at the MHC class II locus, the region is likely similar among the strains of Syrian hamsters available in research
Describe immunoglobulins (Ig) in hamsters.
Thymic system and associated cellular immunity development delayed in Syrian hamsters compared to other rodents.
Only 4 of the 5 Ig have been described in hamsters - IgM, IgG, IgA, and IgE (IgD remains to be defined; at least two inbred strains are deficient in the sixth component of complement)
Another IgG isotype, IgG3 has been isolated from some strains of inbred Syrian hamsters - IgG3 different from IgG1 and IgG2 by its affinity for protein A; immunodeficiency has NOT been linked to deficiencies in IgG3.
First crystal structure of a hamster IgG Fab fragment and the complete cDNA sequence of the stimulatory Ab HL4E10 (contains first examples of hamster lambda light chain) has been identified.
-HL4E10 Ab is uniquely costimulatory for γδ T cells - humanized versions may be of clinical relevance in treating γδ T cell dysfunction-associated dz, such as chronic non-healing wounds and cancer
Describe Harderian glands in hamsters.
Pigmented lacrimal glands located posterior to the ocular globes - release a lipid and porphyrin-rich material that lubricates eyes and eyelids
Also site of immune response, source of thermoregulatory lipids and pheromones, photoprotective organ, part of the retinal-pineal axis
Marked sexual dimorphism in Syrian hamsters (NOT Chinese, Armenian, or Djungarian) - females secrete up to 10^3 times more porphyrin than males & diffs in type of lipid droplets secreted; glandular dimorphism androgen-dependent & has seasonal variation
Describe flank glands in hamsters.
Coarse hair over darkly pigmented skin in the costovertebral area in males - marks dermal structures composed of sebaceous glands that produce secretions in response to androgens - when male sexually excited, hair may appear wet and hamster may seem pruritic - secretions likely for territorial marking
-Females also have dorsal sebaceous glands, but they are not assoc w/ estrous cycle and are harder to identify
Describe hibernation in hamsters.
Hibernation ability varies among species and individual animals.
Exposure to cold stimulates hamsters to gather food; will hibernate at ~5 C +/- 2 C.
European hamster is a TRUE hibernator; Syrian hamster may no reliably enter hibernation at cold temps & bouts of hibernation may be short
Cold exposure and hibernation in the hamster are assoc w/ desaturation of white fat = useful for studies of factors controlling saturation of fat
Describe genetic mutations in Syrian hamsters.
Have diploid chromosome number of 44.
18 mutations of coat and eye color (incl brown, cream, piebald, and white hamsters); 6 mutations of neuromuscular system; 6 mutations of quantity or texture of hair
In 2014, first successful transgenic hamsters created & hamster embryonic stem cell lines have also been created.
What is the typical daily food intake for Syrian hamsters?
5.5-8.9 g. Hamsters are typically feed commercial rodent (mouse and rat) feed; they have normal growth and reproduction on these diets.
Describe differences in hamster nutritional needs vs. mice and rats.
- Soybean meal offers better nutritional efficiency than fish meal for hamsters
- Carbs in diet can induce change in both glucose and lipid metabolism
- Increased requirements for dietary zinc, copper, and potassium compared to rats
- Require sources for many B vitamins and non-nutritive bulk
- Require Vitamin E to prevent myocytolysis (Vit E deficiency plus oxidative stress may play a role in heart disease in hamsters); Vit E can also reduce fatty streak accumulation in hypercholesterolemic hamsters
- Increased rates of survival linked to 20g lacalbumin/100g food
- Can be susceptible to colocolic intussusception within 7-10 days of changing to a semipurified feed
Why must hamsters have feed placed on the floor?
Broad muzzle - feed hoppers not recommended for hamsters, or must be able to allow feed pellets to drop through to cage floor.
- Placement of feed on floor acceptable per federal regulations (CFR 2013)
- Hamsters start to eat solid dry food at 7-10 days of age
What is the typical daily water intake for hamsters?
- 5 mL/100 g body weight
- Provide stainless steel water bottle sippers, b/c hamsters can bite through glass or plastic
- Sipper must be low enough to be accessed by the smallest animal in the cage - nursing pups benefit from water, in addition to milk, to prevent GI issues
Describe unique pharmacology responses in hamsters.
- More sensitive to metabolic effects of corticosteroids
- Less sensitive to histamine
- Very resistant to morphine - no sedative or hypnotic effect
- Susceptible to Clostridium difficile overgrowth following administration of lincomycin, clindamycin, ampicillin, vancomycin, erythromycin, cephalosporins, gentamicin, penicillin
When does sexual maturity begin in hamsters?
Males - ~90g body weight
Female - 6-8 weeks; recommend wait to breed until 90-100 g weight
-Copulation can begin as young as 4 week, but pregnancy unusual before 8 wks
-Reproductive capacity for both genders decreases at ~14 months; senescent females can often breed with younger males, w/ notable increase in defective ova and decreased offspring produced
Describe the estrous cycle in hamsters.
4 days in length
- End of ovulation (usually day 2) noted by copious postovulatory vaginal discharge
- Can be successfully mated on day 3 of cycle
How should hamster mating pairs be established?
House individually for at least 1 wk - male establish cage dominance and female cycle normally
3rd day of cycle introduce female to male’s cage 1-2 hr prior to start of dark cycle - females are receptive for ~16 hr from early evening until mid-afternoon next day
-If mating does not occur within 5 min or female is aggressive, remove female and try pairing a different female
-If mating occurs, pair can be left together until following light cycle; ovulation and fertilization generally occur during early morning hours, and the day of separation is considered day 1 of gestation
-Hamsters can be trio bred w/ 1 male and 2 females in cage for 1-2 weeks - to reduce aggression males should be older than females; check daily for fight wounds
What is gestation length in hamsters?
15-18 days
- After mating female moved to nesting cage for at least 2 days prior and 10 days after parturition; minimize disturbance during pregnancy - both to minimize maternal rejection or cannibalization
- No recent accounts of successful cross-fostering of hamsters and bottle feeding rarely successful
- Females can experience pseudopregnancy after infertile mating - is discharge present on days 5-9 after mating = NOT pregnant; pregnant hamsters have distinct weight gain w/ abdominal distension ~10 days after mating
Describe parturition in hamsters.
Just prior, females become restless & eat, groom, and nest-build
- Increased respiratory rate = litter in next several hours
- Most common day of parturition is 16 days gestation & parturition lasts for more than 3 hr
- Syrian hamsters display abrupt change to maternal behavior in late gestation (unlike gradual onset in mice and rats)
Describe development and management of hamster pups.
- Litter size range: 4-12 pups (6-8 most common)
- Possible to sex pups are birth, but preferable to leave cage undisturbed for 7-10 days; if cage must be disturbed - provide food pellets on cage floor for dam to stuff cheek pouches - may reduce cannibalism of pups; dam may put pups in cheek pouch if stressed and then remove them when calm
- Pups remain with dam until at least 19 days old
- Normal weaning is 21-28 days
- Dam estrous cycle does not resume for 1-8 days after parturition
- Young from different litters can be housed together until 40-50 days old, then need to separate d/t aggression in females; males from same litter can be kept together longer
What are required cage space dimensions for hamsters?
60 g or less: 10 in^2 floor space
>60 g: 13-19 in^2 depending on body weight
Female with litter: ~121 in^2
Cage height must be 6 inches from cage floor to cage top
Describe bedding/caging preferences of hamsters.
Essential to have solid floor for nesting females and young
- Prefer pine shavings over aspen shavings & corn cob and aspen shavings preferred over wood pellets when no nesting material; preferences eliminated when nesting material (paper towel) provided
- Aromatic hydrocarbons in bedding/nesting materials can induce nonspecific hepatic enzymes in hamsters
- Urine output is slight & typically use one corner of cage for elimination
- Provide some sort of burrow or shelter to mimic natural underground burrows; nest material recommended; more burrowing behavior if deeper bedding (40-80 cm depth) vs. shallow (10 cm depth)
- 12-14 hr light cycle; 14 hr required for breeders
What are housing temperature, humidity, and lux level recommendations for hamsters?
68-79 F
30-70% humidity
323 lux (30 foot candles) at 1 m above the floor recommended for rodents
-Hamsters fairly adaptable to cooler temps - pre-hibernation hamsters can prefer temps around 8 C (46 F)
What is the causative agent of proliferative enteritis (transmissible ileal hyperplasia) in hamsters?
Also called regional enteritis, enzootic intestinal adenocarcinoma, ‘wet tail’
Extremely contagious; high morbidity and mortality
Lawsonia intracellularis - G(-), nonspore forming, slightly curved rod (1.5 x 0.35 μm); obligated intracellular bacterium; causes proliferative enteropathy in pigs, ferrets, horses, deer, and rabbits
What are clinical signs of proliferative enteropathy in hamsters?
Watery diarrhea - moist matted fur of tail, perineum, ventral abdomen
Dehydration, inactivity, hunched appearance (abdominal pain), abdominal distension, hypothermia, convulsions just prior to death, rectal prolapse, intussusception
Mortality 50-90%, usually within 48 hr of onset of clinical signs
Chronic cases also reported with mild diarrhea and weight loss
May also be self-limiting without clinical signs
How is proliferative enteritis transmitted in hamsters?
Fecal-oral
Increased severity and development of disease has been assoc w/ overcrowding, transport, surgery, limited and purified diets, transplantation of neoplasms, experimental leishmaniasis
Cross-species transmission has occurred experimentally between swine and hamsters
Vertical transmission has not been evaluated, but unlikely that L. intracellularis can cross placenta
Unknown how long L. intracellularis survives in environment
What are necropsy findings of proliferative enteritis in hamsters?
Gross: segmental thickening and congestion of ileum, enlargement of mesenteric lymph nodes, peritonitis, adhesions
Histology: hyperplasia of columnar mucosal epithelial cells in the terminal ileum, proliferation of glandular epithelium, lymphadenitis with lymphoid hyperplasia, edema, leukocytic infiltration of sinusoids; intestinal crypts may be lengthened with increased mitosis, decreased numbers of goblet cells, and villar atrophy
-L. intracellularis can often identified using Warthin-Starry silver stain in the apical cytoplasm of crypt enterocytes
How is proliferative enteropathy diagnosed in hamsters?
Weanlings are very susceptible - become less susceptible by 6 weeks & resistant to infx by 10 weeks
- Ileum lesions develop in 2 phases: hyperplasia that begins as focal lengthening of villi; ~3 wks following transmission, inflammatory phase with focal necrosis of crypt epithelium
- Particulate bacterial antigen can be detected by immunoperoxidase staining or in situ hybridization in the cytoplasm of mucosal epithelial cells
- Proposed model of bacterial entry: bacteria attach to microvillus brush border - ingestion by endocytosis - release from vacuoles into the cytoplasm of cell - bacteria multiple within cell prior to cell rupture
- Serum antibodies specific for intracytoplasmic antigen
- PCR of feces
What are differential diagnoses for proliferative enteritis in hamsters?
Tyzzer’s disease (Clostridium piliforme), Clostridium difficile enterotoxemia, salmonellosis
-Described changes in ILEUM are pathognomonic for proliferative enteritis
