Phenotypes Associated with This Genotype

Genotype
MGI:3761832

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Soat1^tm1Far/Soat1^tm1Far
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J

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

Apoe^tm1Unc/Apoe^tm1Unc Soat1^tm1Far/Soat1^tm1Far mice display severe xanthomatosis

homeostasis/metabolism

abnormal cholesterol homeostasis ( J:61147 )

abnormal cholesterol level ( J:61147 )

• free cholesterol content of the skin is 6- to 7-fold higher than in single Apoe mutant controls at 4 months of age

decreased circulating cholesterol level ( J:61147 )

• by 120 days of age, mean serum cholesterol levels are lower in double mutants than in single Apoe homozygotes fed a chow diet; disparity in cholesterol levels is more marked and occurs at an earlier age in mutants fed a Western diet

decreased circulating VLDL cholesterol level ( J:61147 )

• reduced VLDL and IDL cholesterol compared to single Apoe homozygotes

xanthoma ( J:61147 )

• mutants fed a Western diet exhibit a massive cholesterol xanthoma by 3-4 months of age

• free cholesterol crystal deposits are seen in brains of mutants fed a Western diet for 3 months, mostly near the choroid plexus

cardiovascular system

atherosclerotic lesions ( J:61147 )

• mutants fed a Western diet develop atherosclerotic lesions, however lesions are smaller than in single Apoe homozygotes

• aortic lesion composition differs from that in Apoe homozygotes, with lower neutral lipid content and fewer cholesterol crystals and a paucity of macrophages in the most advanced lesions

immune system

skin inflammation ( J:61147 )

• cholesterol deposition in the skin is accompanied by a severe, pleomorphic inflammatory cell infiltrate with features of acute and chronic inflammation, including large numbers of neutrophils, multinucleated giant cells with occasional intracellular cholesterol clefts, and frequent mononuclear cells, lymphocytes, and plasma cells

nervous system

abnormal brain morphology ( J:61147 )

• free cholesterol crystal deposits are seen in brains of mutants fed a Western diet for 3 months, mostly near the choroid plexus

integument

skin inflammation ( J:61147 )

• cholesterol deposition in the skin is accompanied by a severe, pleomorphic inflammatory cell infiltrate with features of acute and chronic inflammation, including large numbers of neutrophils, multinucleated giant cells with occasional intracellular cholesterol clefts, and frequent mononuclear cells, lymphocytes, and plasma cells

abnormal coat appearance ( J:61147 )

• by 2-3 months of age, fur appears dull and mutants show pruritus

sparse hair ( J:61147 )

• diffuse hair loss occurs by 5-6 months of age and leads to severe lesions

abnormal skin morphology ( J:61147 )

• free cholesterol content of the skin is 6- to 7-fold higher than in controls at 4 months of age

• mutants fed a Western diet exhibit more severe skin changes and at an earlier age (6 weeks) than wild-type or mutants fed a chow diet

abnormal dermal layer morphology ( J:61147 )

• the dermis exhibits diffuse needle-shaped lucencies indicative of cholesterol crystals; crystals appear predominantly extracellularly and are seen in or below the reticular dermis

• deeper layers of the dermis show marked proliferation of fibroblasts and extensive collagen deposition

thick dermal layer ( J:61147 )

hyperkeratosis ( J:61147 )

• hyperkeratosis at the skin surface

skin lesions ( J:61147 )

• develop severe skin lesions within months when fed a chow diet

abnormal skin condition ( J:61147 )

• by 2-3 months of age, show pruritus

• by 5-6 months of age, excoriation occurs and leads to severe lesions

skin fibrosis ( J:61147 )