Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names Acacttm1F    (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S4 via RF8 ES cell line Generation N11pN1p (09-NOV-05)   Donating Investigator Bob Farese,   Gladstone Inst of Cardiovascular Disease

Description
Mice homozygous for the Soat1^tm1 targeted mutation display tissue specific decreases in cholesterol esterification. Fibroblasts and adrenal membranes of homozygous mutant mice show diminished cholesterol esterification and markedly reduced cholesterol ester levels in adrenal glands and peritoneal macrophages. However, the livers of SOAT1-deficient mice contained substantial amounts of cholesterol esters and exhibited no reduction in cholesterol esterification activity. These findings support the presence of more than one form of esterification enzyme in mammals. A second sterol O-acyltransferase gene (Soat2), expressed in the liver and intestine, has subsequently been identified in mice and humans.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Soat1^tm1Far allele

007147	B6.129S4-Soat1tm1Far/Pgn
002896	B6;129S4-Soat1tm1Far/J

View Strains carrying   Soat1^tm1Far     (2 strains)

Strains carrying other alleles of Soat1

000648

AKR/J

View Strains carrying other alleles of Soat1     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Soat1^tm1Far/Soat1^tm1Far

        involves: 129S4/SvJae * C57BL/6

• endocrine/exocrine gland phenotype
• abnormal adrenal gland morphology (MGI Ref ID J:37049)
  • adrenal glands are translucent and brownish instead of opaque and whitish-yellow as in wild-type and lack neutral lipids
• homeostasis/metabolism phenotype
• abnormal cholesterol homeostasis (MGI Ref ID 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 (MGI Ref ID 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 (MGI Ref ID J:37049)
• abnormal lipid level (MGI Ref ID J:37049)
  • reduction in cholesterol ester levels in adrenal glands and in peritoneal macrophages
• increased circulating cholesterol level (MGI Ref ID 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 (MGI Ref ID J:37049)
• hematopoietic system phenotype
• abnormal macrophage morphology (MGI Ref ID J:37049)
  • reduction in cholesterol ester levels in peritoneal macrophages
• immune system phenotype
• abnormal macrophage morphology (MGI Ref ID J:37049)
  • reduction in cholesterol ester levels in peritoneal macrophages
• liver/biliary system phenotype
• abnormal liver morphology (MGI Ref ID 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

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Soat1^tm1Far related

Cardiovascular Research
Atherosclerosis

Internal/Organ Research
Adrenal Cortex Defects

Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Soat1tm1Far
Allele Name		targeted mutation 1, RV Farese
Allele Type		Targeted (knock-out)
Common Name(s)		Acact-; Acat-1-;
Mutation Made By		Bob Farese,   Gladstone Inst of Cardiovascular Disease
Strain of Origin		129S4/SvJae
ES Cell Line Name		RF8
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Soat1, sterol O-acyltransferase 1
Chromosome		1
Gene Common Name(s)		8430426K15Rik; ACACT; ACAT; ACAT-1; ACAT1; AW550831; Acact; RIKEN cDNA 8430426K15 gene; RP11-215I23.2; SOAT; STAT; acetyl coenzyme A cholesterol acyltransferase; adrenocortical lipid depletion; ald; expressed sequence AW550831;
Molecular Note		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. [MGI Ref ID J:37049]

Genotyping

Genotyping Information

Genotyping Protocols

Soat ^tm1Far, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Meiner VL; Cases S; Myers HM; Sande ER; Bellosta S; Schambelan M; Pitas RE; McGuire J; Herz J; Farese RV Jr. 1996. 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 93(24):14041-6. [PubMed: 8943057]  [MGI Ref ID J:37049]

Additional References

Meiner VL; Welch CL; Cases S; Myers HM; Sande E; Lusis AJ; Farese RV Jr. 1998. Adrenocortical lipid depletion gene (ald) in AKR mice is associated with an acyl-CoA:cholesterol acyltransferase (ACAT) mutation. J Biol Chem 273(2):1064-9. [PubMed: 9422770]  [MGI Ref ID J:42073]

Uelmen PJ; Oka K; Sullivan M; Chang CC; Chang TY; Chan L. 1995. Tissue-specific expression and cholesterol regulation of acylcoenzyme A:cholesterol acyltransferase (ACAT) in mice. Molecular cloning of mouse ACAT cDNA, chromosomal localization, and regulation of ACAT in vivo and in vitro. J Biol Chem 270(44):26192-201. [PubMed: 7592824]  [MGI Ref ID J:29712]

Soat1^tm1Far related

Accad M; Smith SJ; Newland DL; Sanan DA; King LE Jr; Linton MF; Fazio S; Farese RV Jr. 2000. Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1 [see comments] J Clin Invest 105(6):711-9. [PubMed: 10727439]  [MGI Ref ID J:61147]

Cui D; Thorp E; Li Y; Wang N; Yvan-Charvet L; Tall AR; Tabas I. 2007. Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells. J Leukoc Biol 82(5):1040-50. [PubMed: 17576822]  [MGI Ref ID J:127198]

Freeman NE; Rusinol AE; Linton M; Hachey DL; Fazio S; Sinensky MS; Thewke D. 2005. Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages. J Lipid Res 46(9):1933-43. [PubMed: 15995174]  [MGI Ref ID J:100481]

Matynia A; Anagnostaras SG; Wiltgen BJ; Lacuesta M; Fanselow MS; Silva AJ. 2008. A high through-put reverse genetic screen identifies two genes involved in remote memory in mice. PLoS ONE 3(5):e2121. [PubMed: 18464936]  [MGI Ref ID J:136217]

Rodriguez A; Ashen MD; Chen ES. 2005. ACAT1 deletion in murine macrophages associated with cytotoxicity and decreased expression of collagen type 3A1. Biochem Biophys Res Commun 331(1):61-8. [PubMed: 15845358]  [MGI Ref ID J:97572]

Su YR; Dove DE; Major AS; Hasty AH; Boone B; Linton MF; Fazio S. 2005. Reduced ABCA1-mediated cholesterol efflux and accelerated atherosclerosis in apolipoprotein E-deficient mice lacking macrophage-derived ACAT1. Circulation 111(18):2373-81. [PubMed: 15851589]  [MGI Ref ID J:111648]

Su Z; Wang X; Tsaih SW; Zhang A; Cox A; Sheehan S; Paigen B. 2009. Genetic basis of HDL variation in 129/SvImJ and C57BL/6J mice: importance of testing candidate genes in targeted mutant mice. J Lipid Res 50(1):116-25. [PubMed: 18772481]  [MGI Ref ID J:144089]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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