Phenotypes associated with this allele

• Allele Symbol: Soat1^tm1Far
• Allele Name: targeted mutation 1, Bob Farese
• Allele ID: MGI:1857978
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Soat1^tm1Far/Soat1^tm1Far	involves: 129S4/SvJae * C57BL/6	MGI:2174741
cx2	Apoe^tm1Unc/Apoe^tm1Unc Soat1^tm1Far/Soat1^tm1Far	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J	MGI:3761832
cx3	Ldlr^tm1Her/Ldlr^tm1Her Soat1^tm1Far/Soat1^tm1Far	involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6J	MGI:3761833

Genotype
MGI:2174741

hm1

• Allelic Composition: Soat1^tm1Far/Soat1^tm1Far
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

Adrenal lipid depletion in Soat1^tm1Far/Soat1^tm1Far mice

endocrine/exocrine glands

abnormal adrenal gland morphology ( J:37049 )

• adrenal glands are translucent and brownish instead of opaque and whitish-yellow as in wild-type and lack neutral lipids

homeostasis/metabolism

abnormal cholesterol homeostasis ( J:37049 )

• decrease in cholesterol esterification in fibroblasts and adrenal membranes

• esterification activity in fibroblasts is not stimulated in response to cholesterol (human LDL or 25-hydroxycholesterol)

• hepatic cholesterol ester levels are 30% lower in mutants fed a chow diet but are similar to wild-type when fed a high-fat diet

abnormal lipid level ( J:37049 )

• reduction in cholesterol ester levels in adrenal glands and in peritoneal macrophages

increased circulating cholesterol level ( J:37049 )

• on a chow or high-fat diet, mutants have higher plasma levels of total and HDL cholesterol than wild-type

increased circulating HDL cholesterol level ( J:37049 )

hematopoietic system

abnormal macrophage morphology ( J:37049 )

• reduction in cholesterol ester levels in peritoneal macrophages

immune system

abnormal macrophage morphology ( J:37049 )

• reduction in cholesterol ester levels in peritoneal macrophages

liver/biliary system

abnormal liver morphology ( J:37049 )

• hepatic cholesterol ester levels are 30% lower in mutants fed a chow diet but are similar to wild-type when fed a high-fat diet

Genotype
MGI:3761832

cx2

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

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 )

Genotype
MGI:3761833

cx3

• Allelic Composition: Ldlr^tm1Her/Ldlr^tm1Her; Soat1^tm1Far/Soat1^tm1Far
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6J

Soat1^tm1Far/Soat1^tm1Far Ldlr^tm1Her/Ldlr^tm1Her mice fed an atherogenic diet for 2 months display severe xanthomatosis

homeostasis/metabolism

decreased circulating cholesterol level ( J:61147 )

• serum total cholesterol levels in mutants fed the atherogenic diet for 2 months are lower than in single Ldlr homozygotes

skin edema ( J:61147 )

• skin of mutants fed an atherogenic diet shows edematous lesions

xanthoma ( J:61147 )

• double mutants fed an atherogenic diet for 2 months develop severe dermal xanthomatosis; skin shows diffuse deposition of cholesterol crystals in both the reticular and papillary dermis

cardiovascular system

atherosclerotic lesions ( J:61147 )

• mutants fed a Western diet develop atherosclerotic lesions

• aortic lesion composition differs from that in Apoe homozygotes, with lower neutral lipid content and fewer cholesterol crystals

immune system

skin inflammation ( J:61147 )

• severe, pleomorphic inflammatory reaction accompanies the cholesterol deposition in atherogenic diet fed mutants, however the features are different from those in double Soat1 and Apoe mutants

• inflammatory cells are predominantly macrophages, lymphocytes, and plasma cells, with fewer neutrophils than in double Soat1 and Apoe mutants

nervous system

abnormal brain morphology ( J:61147 )

• mutants fed an atherogenic diet exhibit crystalline cholesterol deposits in the brains, particularly near the choroid plexus and in the cerebellum

abnormal cerebellum morphology ( J:61147 )

• mutants fed an atherogenic diet exhibit crystalline cholesterol deposits in the cerebellum

integument

skin edema ( J:61147 )

• skin of mutants fed an atherogenic diet shows edematous lesions

skin inflammation ( J:61147 )

• severe, pleomorphic inflammatory reaction accompanies the cholesterol deposition in atherogenic diet fed mutants, however the features are different from those in double Soat1 and Apoe mutants

• inflammatory cells are predominantly macrophages, lymphocytes, and plasma cells, with fewer neutrophils than in double Soat1 and Apoe mutants

abnormal dermal layer morphology ( J:61147 )

• diffuse deposition of cholesterol crystals in the reticular and papillary dermis of mutants fed an atherogenic diet

skin lesions ( J:61147 )

• skin lesions are seen only when mutants are fed a Western diet and not when fed a chow diet

thick skin ( J:61147 )

• mutants fed an atherogenic diet, but not a chow diet, develop diffuse, massive thickening of the skin compared to single Ldlr mutants

• however, do not develop skin excoriations, hair loss or pruritic skin