Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129S4/SvJae H2 Haplotype b Generation N6pN1

Description
Phenotypically similar to B6.129S4-Soat1^tm1Far/J (003322), B6.129S4-Soat1^tm1Far/Pgn has a reduced congenic interval making the closely linked Apoa2 gene of C57BL/6 rather than 129S4 origin. The donating investigator indicates that HDL levels exhibit a 24% increase on high fat diet in this strain in contrast to the 73% increase observed in the original strain. Triglyceride levels are unchanged. This strain may be useful in atherosclerosis research.

Development
This strain is derived from B6.129S4-Soat1^tm1Far/J (003322) by further backcrossing to C57BL/6 reducing the congenic interval to a region defined by rs4222719 and D1Mit159. The reduced interval excludes the linked gene Apoa2 from the 129S4 derived region. Dr. Beverly Paigen performed the additional backcrosses at The Jackson Laboratory; the strain was cryopreserved in 2007.

Related Strains

Strains carrying   Soat1^tm1Far allele

003322	B6.129S4-Soat1tm1Far/J
002896	B6;129S4-Soat1tm1Far/J

View Strains carrying   Soat1^tm1Far     (2 strains)

Additional Web Information

Congenic Nomenclature

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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

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

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]

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	Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

General Terms and Conditions

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The Jackson Laboratory's Genotype Promise

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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