Rat Models Flashcards
(46 cards)
Metabolic disease
insulin resistance, glucose intolerance, hyperinsulinemia, dyslipidemia, obesity, and hypertension
Obesity
- Zucker Diabetic Fatty
- Spontaneously hypertensive obese rat (SHROB)
- Dietary induced obesity prone rat (DIO)
• Zucker Diabetic Fatty: leptin (recessive) mutation
o Outbred most widely used
• Hyperlipidemia, hypercholesterolemia, hyperinsulinemia
• Doesn’t usually develop Type 2 diabetes
• Spontaneously hypertensive obese rat (SHROB)
o SHR and Sprague Dawley cross
o Hypertriglyceridemia, spontaneous hypertension, hyperinsulinemia, hyperlipidemia
o Absence of leptin receptor leads to obesity
• Dietary induced obesity prone rat (DIO)
o Must be fed high energy/ fat diet
o Model of human obesity, non leptin deficient obesity
Diabetes
Diabetes, Type 1
o BBDP (inbred albino Biomedical Research Models) • Model of spontabeous autoimmune diabetes
Diabetes, Type 2
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
• Chemically induced diabetes
o Streptozotocin: causes Type 1 by destroying pancreatic beta cells in adults and Type 2 in neonates
Hypertension
• 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
Epilepsy
• 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
Multiple Sclerosis
• 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
Parkinson’s Disease
- 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
Cancer
• Prostate cancer: Lobund Wistar Rat (LW)
o Spontaneous or induced with N-methyl-N-nitrosourea/ testosterone
o Noble Rat
• Mammary cancer: Copenhagan, Wistar Furth
Rheumatoid arthritis
• 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
Menopause: cessation of ovarian cyclicity resulting from depletion of ovarian follicles by atresia
• 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
Aortic banding (pressure overload) model of heart failure
- Band ascending and descending aorta in rats to produce severe ventricular hypertrophy after about 12 weeks
- Mimics stenosis of the aortic valve
Stroke
• 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
• End stage renal disease associated with hypertension, diabetes, and polycystic kidney disease
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)
o ZSF1 rat
diabetic nephropathy
o Hypertension and diabetes on renal function
ZDF, SHORB, SHR, SHRSP, Fawn hooded, GH, and Dahl SS/J
• Polycystic kidney disease (Bright’s disease)
o Han: SPRD (Han: Sprague Dawley (Cy/+) rat
• Diabetes Insipidus: neurogenic deficiency of antidiuretic hormone or insensitivity to the antidiuretic hormone
o Kidney does not reabsorb proper amount of water
o Brattleboro rat: neurogenic form (hypothalamus dysfunction)
FANFT- N-[4-(5-Nitro-2-furyl)-2-thiazolyl] formamide: induces 100% incidence of
bladder carcinoma
Coopenhagen (COP) Rat: Strain carries dominant resistance gene
mammary cancer
