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AG_Rats > Rat Models > Flashcards

Rat Models Flashcards

1
Q

Metabolic disease

A

insulin resistance, glucose intolerance, hyperinsulinemia, dyslipidemia, obesity, and hypertension

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2
Q

Obesity

A
  • Zucker Diabetic Fatty
  • Spontaneously hypertensive obese rat (SHROB)
  • Dietary induced obesity prone rat (DIO)
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3
Q

• Zucker Diabetic Fatty: leptin (recessive) mutation

A

o Outbred most widely used
• Hyperlipidemia, hypercholesterolemia, hyperinsulinemia
• Doesn’t usually develop Type 2 diabetes

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4
Q

• Spontaneously hypertensive obese rat (SHROB)

A

o SHR and Sprague Dawley cross
o Hypertriglyceridemia, spontaneous hypertension, hyperinsulinemia, hyperlipidemia
o Absence of leptin receptor leads to obesity

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5
Q

• Dietary induced obesity prone rat (DIO)

A

o Must be fed high energy/ fat diet
o Model of human obesity, non leptin deficient obesity
Diabetes

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6
Q

Diabetes, Type 1

A 
o	BBDP (inbred albino Biomedical Research Models)
•	Model of spontabeous autoimmune diabetes
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7
Q

Diabetes, Type 2

A

o Zucker diabetic fatty (inbred, hooded black and white)
• Primary model for Type 2 and effects on wound healing, periodontal disease, and neuropathy
• Females develop diabetes only on a different diet than do males
o Cohen diabetic rat and Goto Kakizaki (GK) rat
• Not obese
o Otsuka Long Evans Tokushima Fatty Rat
• Late onset of hyperglycemia with dev of Type 2 at 18 weeks of age then around 40 weeks of age Type 1 develops

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8
Q

• Chemically induced diabetes

A

o Streptozotocin: causes Type 1 by destroying pancreatic beta cells in adults and Type 2 in neonates

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9
Q

Hypertension

A

• Spontaneous hypertensive rat (SHR, albino, inbred)
o Insulin resistant as well
o WKY is used as control
• Genetically hypertensive rat (GH)
o Model of spontaneous hypertension
• Fawn hooded hypertensive rat (FHH)
o Spontaneous mutation of a Long Evans rat
o Renal damage in SHR
o All fawn hooded strains have hereditary bleeding disorder due to platelet pool deficiency
• Salt sensitive hypertension (Dahl-SS)
o SR/Jr is resistant
o High salt diet for 3-4 wks leads to hypertension and marked vascular and renal lesions
• Surgically induced renovascular hypertension- calmps of renal arteries

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10
Q

Epilepsy

A

• Genetically Epilepsy Prone Rats (GEPR/3 and GEPR/9)
o Dev from outbred Sprague Dawley by selecting for susceptibility to audiogenic induced seizures
• WAG/Rjj Rat (inbred, albino)
o Absence epilepsy
• Genetic absence epilepsy rat from Strasboug (GAERS)
o Generalized, nonconvulsive epileptic seizures

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11
Q

Multiple Sclerosis

A 
•	Experimental autoimmune encephalomyelitis: demyelinating lesions in the CNS from a Th1 inflammatory response
o	Lewis (LEW) and Dark Agouti (DA)
o	Induced with myelin basic protein +/- incomplete Freund’s adjuvant
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12
Q

Parkinson’s Disease

A
  • Dopamine depletion through administration of 6-hydroxydopamine bilaterally into the nucleus accumbens septi
  • Langston model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
  • Rotenone administration
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13
Q

Cancer

A

• Prostate cancer: Lobund Wistar Rat (LW)
o Spontaneous or induced with N-methyl-N-nitrosourea/ testosterone
o Noble Rat
• Mammary cancer: Copenhagan, Wistar Furth

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14
Q

Rheumatoid arthritis

A

• Chronic autoimmune disease with inflammation of joint linings and=/or other internal organs
• Models
o Collagen induced arthritis model
• Complete or incomplete Freund’s adjuvant or pristine
• Develop autoimmune mediated polyarthritis
• LEW and DA commonly used
o Adjuvant induced arthritis model

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15
Q

Menopause: cessation of ovarian cyclicity resulting from depletion of ovarian follicles by atresia

A

• Primordial follicles are a finite pool of oocytes arrested in meiosis
o Progress from primordial to ovulatory stages after puberty
o Most follicles undergo cell death by atresia
o Pool of primordial follicles becomes depleted and ovarian failure (menopause) occurs
• Surgical ovariectomy dot not mimic natural menopause as ovarian steroid hormone production is altered
o Androgens still produced by ovary post menopause
o Just stops producing estradiol
• IP 4-vinycyclohexene works in mice and IP 4-vinyl-1-cyclohexene diepoxide works in mice/ rats
Rheumatoid arthritis

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16
Q

Aortic banding (pressure overload) model of heart failure

A
  • Band ascending and descending aorta in rats to produce severe ventricular hypertrophy after about 12 weeks
  • Mimics stenosis of the aortic valve
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17
Q

Stroke

A

• SHR A1 and A3 substrains: model of hypertension and cerebrovascular disease
• Spontaneous hypertensive heart failure rat (SHHF)
o Model of obesity, Type 2 diabetes, and congestive heart failure
• Surgical myocardial infarction: ligate left anterior descending coronary artery

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18
Q

• End stage renal disease associated with hypertension, diabetes, and polycystic kidney disease

A

o Diabetes and hypertension results in an increase in glomerular filtration rate, proteinuria, and glomerular lesions
o Renal disease associated with metabolic syndrome (hypoinsulinemia, hyperinsulinemia, impaired glucose tolerance)

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19
Q

o ZSF1 rat

A

diabetic nephropathy

20
Q

o Hypertension and diabetes on renal function

A

ZDF, SHORB, SHR, SHRSP, Fawn hooded, GH, and Dahl SS/J

21
Q

• Polycystic kidney disease (Bright’s disease)

A

o Han: SPRD (Han: Sprague Dawley (Cy/+) rat

22
Q

• Diabetes Insipidus: neurogenic deficiency of antidiuretic hormone or insensitivity to the antidiuretic hormone

A

o Kidney does not reabsorb proper amount of water

o Brattleboro rat: neurogenic form (hypothalamus dysfunction)

23
Q

FANFT- N-[4-(5-Nitro-2-furyl)-2-thiazolyl] formamide: induces 100% incidence of

A

bladder carcinoma

24
Q

Coopenhagen (COP) Rat: Strain carries dominant resistance gene

A

mammary cancer

25
Q

Wistar-Furth (WF) Rat: Susceptible to inducible carcinomas.

A

mammary cancer

26
Q

Chemically induced via dimethylbenzanthrecene (DMBA)*

A

mammary cancer

27
Q

Lobund-Wistar (LW):

A

only rat strain genetically predisposed to spontaneous metastasizing, sex hormone- influenced adenocarcinoma*. prostate

28
Q

2 ways to develop model in LW rats Lobund Wistar prostate adenocarcinoma

A

1) Spontaneous (takes 26 months) or 2) ENU + testosterone* (take 10.5 months). The latter stage “premalignant/chem induced” is susceptible to intervention, but late-onset spontaneous is not

29
Q

Noble Rat*:

A

Inbred, black hooded. Chemically induced with testosterone and 17-B-estradiol capsules implanted capsules for 16 wks→ hyperplasia of DL prostate. Longer exposures→ 100% get prostatic carcinomas

30
Q

4-vinycyclohexene

A

chemically induced menopause (destroys ovarian follicles) in mouse ONLY

31
Q

vinyl-1-cyclohexene diepoxide (VCD)

A

chemically induced menopause (destroys ovarian follicles) in rats AND mice

32
Q

rheumatoid arthritis Type II collagen-induced:**

A

DA (Dark Agouti) and BB (DR)/Wor = very susceptible LEW = not susceptible

33
Q

rheumatoid arthritis, adjuvant induced

A

CFA or ICF, pristane, streptococcal cell wall extracts. LEW – very susceptible to streptococcal wall isolates

34
Q

Surgically Induced Myocardial Infarction in Rats:**:

A

ligation of the LAD (left anterior descending) coronary artery
Works because rat doesn’t have a large left circumflex branch*, but difficult to predict when CHF will occur. Almost 100% rat model (vs. mice).

35
Q

Spontaneous Hypertensive Heart Failure Rat

A

Model of obesity, Type II DM and CHF

36
Q

Brattleboro Rat

A

This is an outbred, hooded rat model of hereditary hypothalamic diabetes insipidus→ demonstrates neurogenic characteristics. Main features: High plasma renin activity, high angiotensin II, spontaneous hypertension, abnormally large volume of dilute urine (d/t lack of vasopressin)

37
Q

DBA/2 mice

A

:** Young mice are susceptible to audiogenic seizures which decreases as they reach adulthood
Dilute, brown, non-agouti

38
Q

Parkinson’s Disease**

A

• Characterized by loss of ~50–70% of dopaminergic neurons in the substantia nigra pars compacta, loss of dopamine (DA) in the
striatum & presence of intracytoplasmic inclusions called Lewy bodies (LB), composed mainly of α-synuclein * & ubiquitin

39
Q

Parkinson’s C/S

A

• Main features are motor manifestations (tremors, rigidity, bradykinesia, & postural instability) however, non-motor (olfactory deficits, sleep impairment & neuropsychiatric disorders) may also be present

40
Q

o 6-OHDA

A

Oxidopamine, also known as 6-hydroxydopamine (6-OHDA) or 2,4,5-trihydroxyphenethylamine

irrerversible Parkinson’s

41
Q

o MPTP

A

1 methyl-4-phenyl- 1, 2, 3, 6- tetrahydropyridine

irreversible Parkinson’s

42
Q

rodent Parkinson’s

A

) Mouse or Rat: Induction with 6-OHDA or rotenone. See classic brain pathology and motor phenotype.
Note: Minimal disease in rodents using MPTP (1 methyl-4-phenyl- 1, 2, 3, 6- tetrahydropyridine aka Langston model). This is in contrast to NHPs (OW NHPs more sensitive than NW, older more sensitive than younger!!) Read chapter NHP BB Vol II Ch 15.*

43
Q

Spontaneous Hypertensive Rat (SHR)**

A
  • Developed from WKY outbred (female with severe hypertension x male with mild)→ bred for high BP w/o diet or environ stimuli
  • Most popular rat hypertension model*
  • Polygenic (at least 3 genes responsible for high BP). BP ~ 150 mmHG at 10 wks.
  • Some SHR sub-lines are also stroke prone
  • Excellent for screening anti-hypertension drugs
  • Insulin resistant
  • WKY rat is considered a SHR control*, but is only 50% homologous; other normotensive strains might be equally appropriate
44
Q

Non-Obese Diabetic (NOD) Mouse**

A
  • Best mouse model of spontaneous autoimmune insulin dependent Type I DM
  • Analogous to BBDP/Wor (Bio-Breeding (BB) Diabetic Prone) Rat
45
Q

) Otsuka Long Evans Tokushima Fatty (OLETF) Rat*

A

• Model of Type I DM (pancreatic islets destroyed at wk 40)

46
Q

Goldblatt kidney

A

o Two kidney, one clamp model = Goldblatt kidney

• High rennin model of hypertension

AG_Rats (5 decks)

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