Comparison of featured JAX® Mice for cardiovascular research

Atherosclerosis and Dyslipidemia

B6.129P2-Apoe^tm1Unc/J 

002052

• One of the most relevant models for atherosclerosis research
• Hypercholesterolemic and spontaneously develop arterial lesions
• Atherosclerosis progression very similar to that in humans
• By 3 months, homozygotes develop fatty streaks in the proximal aorta
• Develop lesions more quickly if fed a Western diet (containing 21% fat and 0.15% cholesterol), and even more quickly if fed a high-cholesterol diet (containing 15% fat, 1.25% cholesterol, and 0.5% cholic acid)
• With age, develop more lesions with relatively less lipid but more elongated cells, typical of the advanced stage pre-atherosclerotic lesions (Jawien et al. 2004)
• Extensive phenotypic data available from the Mouse Phenome Database

B6.129S7-Ldlr^tm1Her/J 

002207

• High serum cholesterol levels (200-400 mg/dl) on regular chow diet
• Very high levels (> 2,000 mg/dl) when fed a high fat diet (normal levels are 80-100 mg/dl)
• Develop small atherosclerotic lesions spontaneously but slowly when fed chow
• Lesions develop much faster when fed either high cholesterol or Western diet (Jawien et al. 2004)

C57BL/6J 

000664

• Highly susceptible to diet-induced atherosclerosis: after feeding an atherogenic diet (15% fat, 1.25% cholesterol and 0.5% sodium cholate) for 12 weeks, both young and old mice develop moderate hypercholesterolemia and form fatty streaks at the aortic root (Li et al. 2008)
• Highly susceptible to diet-induced obesity
• The most widely used, best characterized, and only fully sequenced inbred mouse strain
• Part of our unique Genetic Stability Program, which effectively stops cumulative genetic drift
• Extensive phenotypic data available from the Mouse Phenome Database

C57L/J 

000668

• Highly susceptible to diet-induced atherosclerosis: after feeding an atherogenic diet (15% fat, 1.25% cholesterol and 0.5% sodium cholate) mice develop atherosclerotic aortic lesions (Paigen et al. 1990)
• Susceptible to diet-induced gallstones (Xu et al. 2004)
• Extensive phenotypic data available from the Mouse Phenome Database

SM/J 

000687

• Highly susceptible to diet-induced atherosclerosis: after feeding an atherogenic diet (15% fat, 1.25% cholesterol and 0.5% sodium cholate) mice develop atherosclerotic aortic lesions (Paigen et al. 1990)
• Susceptible to diet-induced obesity
• Extensive phenotypic data available from the Mouse Phenome Database

C57BL/6-Tg(APOA1)1Rub/J 

001927

• High concentration of APOA1 in the artery wall likely enhances cellular cholesterol efflux and protects against atherosclerosis
• Homozygotes viable, fertile, and normal-sized
• Twice as much total plasma cholesterol but over four times less mouse APOAI than normal
• Resistant to diet-induced fatty streak lesions (Rubin et al. 1991)

B6.129P2-Apoa1^tm1Unc/J 

002055

• Homozygotes appear to develop normally despite having no APOA1 protein
• After being fasted overnight, exhibit severely reduced levels of plasma cholesterol and HDL-cholesterol
• Deficient in alpha-migrating HDL particles (Williamson et al. 1992)
• Cholesterol absorption slow and significantly reduced (Iqbal and Hussain 2005)

Hypertension and Hypotension

B6.129P2-Nos3^tm1Unc/J 

002684

• Blood pressure approximately 20 mmHg higher than that of normal wild-type siblings
• Low heart rate (Bradycardia)
• Insulin resistant in the liver and peripheral tissues (Shesely et al. 1996)

BPH/2J, BPL/1J, BPN/3J 

003005, 003006, 003004

• Descendants from an 8-way cross from which hypertensive and hypotensive mouse lines were selected (Schlager and Sides 1997)
• BPH/2J is hypertensive: by 5 weeks, has high systolic blood pressures; by 150 days, blood pressure is 60mmHg higher than BPL/1J; higher heart rate, larger hearts and kidneys, and higher hematocrit counts than BPL/1J; lower renin, aldosterone, and angiotensin levels than BPL/1J and BPN/3J
• BPL/1J is hypotensive
• BPN/3J is normotensive: inbred at the same time as and from the same parental strain as BPL/1J and BPN/3J, but in the absence of any selection pressure; normotensive control for BPH/2J and BPL/1J
• 3-5 genes likely responsible for the difference in blood pressures between BPH/2 and BPL/1 mice (Schlager and Sides 1997; Uddin and Harris-Nelson 2004)
• Observations by JAX scientists (Paigen and Svenson, pers. comm.) suggest that BPH/2J may be a model of preeclampsia: appears to have several preeclampsia phenotypes, including small litters of 1-2 pups (Dokras et al. 2006; Davisson et al. 2002)
• Phenotypic data for BPH/2J, BPL/1J, and BPN/3J available from the Mouse Phenome Database

129S/SvEv-Tg(Alb1-Ren)1Unc/CofJ

007853

• Hemizygotes have very high blood pressure, polydipsia, polyuria, proteinuria, and kidney damage
• Cardiac hypertrophy with fibrosis and 50% male mortality between 6-8 months, due to increased circulating levels of angiotensin II High ectopic levels of active mouse renin in the liver and high plasma levels of prorenin and active renin
• May be used to study the effects of genetically clamped renin (and angiotensin II) on hypertension, diabetic nephropathy, albuninurea, nephrosclerosis, and other cardiovascular disorders (Caron et al. 2002, 2004)

Heart Disorders

B6.129P2-Nos3^tm1Unc/J 

002684

• Low heart rate (Bradycardia)
• Blood pressure approximately 20 mmHg higher than that of normal wild-type siblings
• Insulin resistant in the liver and peripheral tissues (Shesely et al. 1996)

129S/SvEv-Tg(Alb1-Ren)1Unc/CofJ 

007853

• Hemizygotes have very high blood pressure, polydipsia, polyuria, proteinuria, and kidney damage
• Cardiac hypertrophy with fibrosis and 50% male mortality between 6-8 months, due to increased circulating levels of angiotensin II
• High ectopic levels of active mouse renin in the liver and high plasma levels of prorenin and active renin
• May be used to study the effects of genetically clamped renin (and angiotensin II) on hypertension, diabetic nephropathy, albuninurea, nephrosclerosis, and other cardiovascular disorders (Caron et al. 2002, 2004)

B6.129-Fbn1^tm1Hcd/J 

012885

• Cys1039Tyr mutation is similar to the human mutation that underlies classic Marfan syndrome
• Heterozygotes develop proximal aortic aneurysms, mitral valve thickenings, pulmonary alveolar septation defects, mild thoracic kyphosis, and skeletal myopathy

• Most heterozygotes (90%) live to one year of age