Mouse Genome Informatics
hm
    Apoetm3(APOE*4)Mae/Apoetm3(APOE*4)Mae
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
growth/size
• weight gain slows down after 4 weeks on high fat diets relative to Apoetm2(APOE*3)Mae

homeostasis/metabolism
• reduced insulin stimulated glucose uptake by epididymal fat
• after 2 months on a high fat diet
• slower clearance of lipid from the blood after ingestion
• relative to Apoetm2(APOE*3)Mae regardless of diet
• relative to Apoetm2(APOE*3)Mae regardless of diet
• increased cholesterol/fatty acid ratio on a normal diet relative to Apoetm2(APOE*3)Mae
• increased diameter of VLDL particles relative to Apoetm2(APOE*3)Mae
• reduced clearance of Apoe deficient VLDL relative to Apoetm2(APOE*3)Mae
• in the HDL fraction relative to ApoeApoetm2(APOE*3)Mae regardless of diet
• relative to Apoetm2(APOE*3)Mae regardless of diet

cardiovascular system
• lesion size twice that in Apoetm2(APOE*3)Mae mice after 3 months on an atherogenic diet
• 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
• fewer small adipocytes
• less epididymal fat than in Apoetm2(APOE*3)Mae mice

immune system
• in response to lipopolysaccharide injection, peaking after 3 hours
• in response to lipopolysaccharide injection, peaking after 1 hour
• higher level of HSV-1 shedding 6 days after ocular infection
• higher numbers of virus in the trigeminal nerve than in controls

vision/eye
• 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
• 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
• atrophy of the retinal pigment epithelium is seen in aged mutants fed a high-fat diet
• corneal hazing 9 days after ocular infection with HSV-1
• stromal opacity in 70% of mice by day 11
• 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
• aged (65-127 weeks) mutants fed a high-fat diet exhibit thinning of the outer nuclear layer

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

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

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

Mouse Models of Human Disease
OMIM IDRef(s)
Macular Degeneration, Age-Related, 1; ARMD1 603075 J:101147