Soat1<tm1Far> Targeted Allele Detail MGI Mouse (MGI:1857978)

Soat1^tm1Far
Targeted Allele Detail

Nomenclature

Symbol:	Soat1^tm1Far
Name:	sterol O-acyltransferase 1; targeted mutation 1, RV Farese
MGI ID:	MGI:1857978
Synonyms:	Acact-, Acat-1-
Gene:	Soat1 Location: Chr1:158358239-158404459 bp, - strand Genetic Position: Chr1, 81.6 cM

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

Show the 4 image(s) involving this allele.

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:37049
Parent Cell Line:	RF8 (ES Cell)
Strain of Origin:	129S4/SvJae

Mutation
description

Allele Type:	Targeted (knock-out)
Mutation:	Insertion
	Insertion of a neomycin cassette into a 5' early exon (amino acids 50-100). Reduced levels of a truncated mRNA transcript were detected by Northern blot on RNA from preputial glands. No protein was detected by immunoblot analysis in homogenates from preputial glands, ovaries and adrenals. (J:37049)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 3 strains available Cell Lines: 0 lines available
Carrying any Soat1 Mutation:	10 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	cx2	cx3
cardiovascular system			√	√
atherosclerotic lesions			√	√
		hm1	cx2	cx3
endocrine/exocrine glands		√
abnormal adrenal gland morphology		√
		hm1	cx2	cx3
hematopoietic system		√
abnormal macrophage morphology		√
		hm1	cx2	cx3
homeostasis/metabolism		√	√	√
abnormal cholesterol homeostasis		√	√
abnormal cholesterol level			√
increased circulating cholesterol level		√
increased circulating HDL cholesterol level		√
decreased circulating cholesterol level			√	√
decreased circulating VLDL cholesterol level			√
abnormal lipid level		√
xanthoma			√	√
skin edema				√
		hm1	cx2	cx3
immune system		√	√	√
abnormal macrophage morphology		√
skin inflammation			√	√
		hm1	cx2	cx3
liver/biliary system		√
abnormal liver morphology		√
		hm1	cx2	cx3
nervous system			√	√
abnormal brain morphology			√	√
abnormal cerebellum morphology				√
		hm1	cx2	cx3
other phenotype			√
fibrosis			√
		hm1	cx2	cx3
skin/coat/nails			√	√
skin inflammation			√	√
abnormal coat appearance			√
partial hair loss			√
abnormal skin condition			√
skin lesions			√	√
skin edema				√
thick skin				√
abnormal skin morphology			√
abnormal dermal layer morphology			√	√
thick dermal layer			√
hyperkeratosis			√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Soat1^tm1Far/Soat1^tm1Far	involves: 129S4/SvJae * C57BL/6
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 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) abnormal lipid level (J:37049) reduction in cholesterol ester levels in adrenal glands and in peritoneal macrophages 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	Allelic Composition	Genetic Background
cx2	Apoe^tm1Unc/Apoe^tm1Unc Soat1^tm1Far/Soat1^tm1Far	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J
Apoe^tm1Unc/Apoe^tm1Unc Soat1^tm1Far/Soat1^tm1Far mice display severe xanthomatosis skin/coat/nails 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 partial hair loss (J:61147) diffuse hair loss occurs by 5-6 months of age and leads to severe lesions 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 lesions (J:61147) develop severe skin lesions within months when fed a chow diet 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 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 other phenotype fibrosis (J:61147) skin fibrosis 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
Genotype	Allelic Composition	Genetic Background
cx3	Ldlr^tm1Her/Ldlr^tm1Her Soat1^tm1Far/Soat1^tm1Far	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 skin/coat/nails 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 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 abnormal dermal layer morphology (J:61147) diffuse deposition of cholesterol crystals in the reticular and papillary dermis of mutants fed an atherogenic diet 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

References

Original:	J:37049 Meiner VL et al., "Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: evidence suggesting multiple cholesterol esterification enzymes in mammals." Proc Natl Acad Sci U S A 1996 Nov 26;93(24):14041-6
All:	8 reference(s)

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