Phenotypes Associated with This Genotype

Genotype
MGI:4355227

• Allelic Composition: Apoe^{tm3(APOE*4)Mae}/Apoe^{tm3(APOE*4)Mae}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

growth/size/body

abnormal postnatal growth ( J:151284 )

• weight gain slows down after 4 weeks on high fat diets relative to Apoe^{tm2(APOE*3)Mae}

homeostasis/metabolism

amyloid beta deposits ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit perivascular amyloid beta immunoreactivity in the eyes indicating amyloid beta deposits

abnormal glucose homeostasis ( J:151284 )

• reduced insulin stimulated glucose uptake by epididymal fat

impaired glucose tolerance ( J:151284 )

• after 2 months on a high fat diet

abnormal lipid level ( J:74417 )

abnormal circulating lipid level ( J:151284 )

• slower clearance of lipid from the blood after ingestion

decreased circulating HDL cholesterol level ( J:74417 )

• relative to Apoe^{tm2(APOE*3)Mae} regardless of diet

increased circulating VLDL cholesterol level ( J:74417 )

• relative to Apoe^{tm2(APOE*3)Mae} regardless of diet

• increased cholesterol/fatty acid ratio on a normal diet relative to Apoe^{tm2(APOE*3)Mae}

• increased diameter of VLDL particles relative to Apoe^{tm2(APOE*3)Mae}

• reduced clearance of Apoe deficient VLDL relative to Apoe^{tm2(APOE*3)Mae}

decreased circulating triglyceride level ( J:74417 )

• in the HDL fraction relative to ApoeApoe^{tm2(APOE*3)Mae} regardless of diet

increased circulating VLDL triglyceride level ( J:74417 )

• relative to Apoe^{tm2(APOE*3)Mae} regardless of diet

cardiovascular system

increased susceptibility to atherosclerosis ( J:74417 )

• lesion size twice that in Apoe^{tm2(APOE*3)Mae} mice after 3 months on an atherogenic diet

retina neovascularization ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit neovascularization, ranging from mild neovascularization confined to an area adjacent to the RPE and Bruch's membrane to more extensive neovascularization that extends through the RPE and subretinal space and into the neural retina

• some aged miced fed a high-fat diet exhibit extensive neovascular lesions that involve the outer retinal vasculature

adipose tissue

abnormal fat cell morphology ( J:151284 )

• fewer small adipocytes

abnormal epididymal fat pad morphology ( J:151284 )

• less epididymal fat than in Apoe^{tm2(APOE*3)Mae} mice

immune system

increased interleukin-6 secretion ( J:86768 )

• in response to lipopolysaccharide injection, peaking after 3 hours

increased tumor necrosis factor secretion ( J:86768 )

• in response to lipopolysaccharide injection, peaking after 1 hour

abnormal response to infection ( J:138241 )

• higher level of HSV-1 shedding 6 days after ocular infection

• higher numbers of virus in the trigeminal nerve than in controls

vision/eye

retina neovascularization ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit neovascularization, ranging from mild neovascularization confined to an area adjacent to the RPE and Bruch's membrane to more extensive neovascularization that extends through the RPE and subretinal space and into the neural retina

• some aged miced fed a high-fat diet exhibit extensive neovascular lesions that involve the outer retinal vasculature

abnormal retina pigment epithelium morphology ( J:101147 )

• mutants that develop neovascularization show capillaries present on the RPE

• aged (65-127 weeks) mutants fed a high-fat diet exhibit severe retinal pigment epithelium (RPE) changes, including RPE hyperpigmentation, hypopigmentation and atrophy resulting in a thinner RPE cell layer, thick sub-RPE basal deposits and soft drusenoid deposits rich in neutral lipids

• RPE migration and proliferation are seen in areas of vascular invasion of the retina in aged mutants fed a high-fat diet

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

retina pigment epithelium atrophy ( J:101147 )

• atrophy of the retinal pigment epithelium is seen in aged mutants fed a high-fat diet

corneal opacity ( J:138241 )

• corneal hazing 9 days after ocular infection with HSV-1

• stromal opacity in 70% of mice by day 11

thin retina outer nuclear layer ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit thinning of the outer nuclear layer

retina degeneration ( J:101147 )

abnormal Bruch membrane morphology ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit Bruch's membrane thickening

• mutants that develop neovascularization show regions of thinning or loss of Bruch's membrane and capillaries present on choroidal sides of Bruch's membrane

nervous system

amyloid beta deposits ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit perivascular amyloid beta immunoreactivity in the eyes indicating amyloid beta deposits

pigmentation

abnormal retina pigment epithelium morphology ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit severe retinal pigment epithelium (RPE) changes, including RPE hyperpigmentation, hypopigmentation and atrophy resulting in a thinner RPE cell layer, thick sub-RPE basal deposits and soft drusenoid deposits rich in neutral lipids

• RPE migration and proliferation are seen in areas of vascular invasion of the retina in aged mutants fed a high-fat diet

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

• mutants that develop neovascularization show capillaries present on the RPE

retina pigment epithelium atrophy ( J:101147 )

• atrophy of the retinal pigment epithelium is seen in aged mutants fed a high-fat diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration 1		DOID:0110014	OMIM:603075	J:101147