Phenotypes Associated with This Genotype

Genotype
MGI:3695702

• Allelic Composition: Apoe^{tm1(APOE*2)Mae}/Apoe^{tm1(APOE*2)Mae}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cardiovascular system

atherosclerotic lesions ( J:48565 )

• all spontaneously develop atherosclerotic plaques in the proximal aorta, even on a regular diet

increased susceptibility to atherosclerosis ( J:48565 )

• an atherogenic diet, high in fat and cholesterol, exacerbates development of atherosclerosis

homeostasis/metabolism

abnormal lipid homeostasis ( J:48565 , J:67282 )

• delay in clearance of beta-migrating VLDL particles (J:48565)

• accumulation of beta-VLDL particles in plasma; more than 65% of the total cholesterol is in the VLDL-intermediate density lipoprotein range (J:48565)

• beta-VLDL particles are highly enriched in cholesterol ester and have a VLDL cholesterol-to-triglyceride ratio of 0.76 compared with 0.03 in Apoe^tm2(APOE)Mae homozygotes (J:48565)

• unable to clear VLDL from plasma completely 4 hours post-injection (J:67282)

abnormal lipid level ( J:48565 , J:67282 )

• develop type III hyperlipoproteinemia, even on a low low-fat and low-cholesterol diet (J:48565)

increased circulating cholesterol level ( J:48565 , J:67282 )

• plasma cholesterol levels are 2-3 times those of controls, however HDL cholesterol levels are no different from controls (J:48565)

increased circulating triglyceride level ( J:48565 , J:67282 )

• plasma triglyceride levels are 2-3 times those of controls (J:48565)

hyperlipidemia ( J:48565 )

• develop hyperlipidemia, even on a low-fat and low-cholesterol diet

• an atherogenic diet, high in fat and cholesterol, exacerbates the hyperlipidemia

xanthoma ( J:48565 )

• an atherogenic diet, high in fat and cholesterol, exacerbates development of xanthomas; the atherogenic diet causes swelling of the carpi, paws, and periorbital area and a dramatic deposition of lipid under the skin

liver/biliary system

liver/biliary system phenotype ( J:48565 )

N • livers of mutants on the atherogenic diet appear normal compared to wild-type which are enlarged and pale, indicating protection of hepatocytes from fatty changes

pigmentation

abnormal retina pigment epithelium morphology ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit retinal pigment epithelium (RPE) changes such as RPE vacuolization, RPE mottling, including hyperpigmentation and hypopigmentation and Bruch's membrane thickening

• aged mutants fed a high-fat diet exhibit accumulation of deposits between the RPE and Bruch's membrane of varying thickness and RPE basal infoldings that are disorganized or absent

vision/eye

abnormal retina pigment epithelium morphology ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit retinal pigment epithelium (RPE) changes such as RPE vacuolization, RPE mottling, including hyperpigmentation and hypopigmentation and Bruch's membrane thickening

• aged mutants fed a high-fat diet exhibit accumulation of deposits between the RPE and Bruch's membrane of varying thickness and RPE basal infoldings that are disorganized or absent

retina degeneration ( J:101147 )

abnormal Bruch membrane morphology ( J:101147 )

• thickening of Bruch's membrane