Soat1

Summary

Gene Symbol: Soat1
Description: sterol O-acyltransferase 1
Alias: 8430426K15Rik, ACAT-1, AW550831, Acact, ald, hid, sterol O-acyltransferase 1, acyl-coenzyme A:cholesterol acyltransferase 1, adrenocortical lipid depletion, cholesterol acyltransferase 1
Species: mouse
Products:     Soat1

Top Publications

  1. Wang S, Shi W, Wang X, Velky L, Greenlee S, Wang M, et al. Mapping, genetic isolation, and characterization of genetic loci that determine resistance to atherosclerosis in C3H mice. Arterioscler Thromb Vasc Biol. 2007;27:2671-6 pubmed
    ..We have also determined that Tlr4 on the C3H ApoE(-/-) background does not contribute to early lesion development. *Ath29 is referred to as Ath22 in Su et al 2006. ..
  2. Rice R, Rocke D, Tsai H, Silva K, Lee Y, Sundberg J. Distinguishing mouse strains by proteomic analysis of pelage hair. J Invest Dermatol. 2009;129:2120-5 pubmed publisher
    AKR/J mice display a hair interior defect (hid) phenotype for which the molecular basis is unknown...
  3. Yagyu H, Kitamine T, Osuga J, Tozawa R, Chen Z, Kaji Y, et al. Absence of ACAT-1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia. J Biol Chem. 2000;275:21324-30 pubmed
    ..These results indicate that the local inhibition of ACAT activity in tissue macrophages is protective against cholesteryl ester accumulation but causes cutaneous xanthomatosis in mice that lack apo E or LDLR. ..
  4. Su Y, Dove D, Major A, Hasty A, Boone B, Linton M, et al. Reduced ABCA1-mediated cholesterol efflux and accelerated atherosclerosis in apolipoprotein E-deficient mice lacking macrophage-derived ACAT1. Circulation. 2005;111:2373-81 pubmed
    Macrophage acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1) and apolipoprotein E (apoE) have been implicated in regulating cellular cholesterol homeostasis and therefore play critical roles in foam cell formation...
  5. Su Z, Li Y, James J, McDuffie M, Matsumoto A, Helm G, et al. Quantitative trait locus analysis of atherosclerosis in an intercross between C57BL/6 and C3H mice carrying the mutant apolipoprotein E gene. Genetics. 2006;172:1799-807 pubmed
  6. Rice R, Bradshaw K, Durbin Johnson B, Rocke D, Eigenheer R, Phinney B, et al. Differentiating inbred mouse strains from each other and those with single gene mutations using hair proteomics. PLoS ONE. 2012;7:e51956 pubmed publisher
  7. Matynia A, Anagnostaras S, Wiltgen B, Lacuesta M, Fanselow M, Silva A. A high through-put reverse genetic screen identifies two genes involved in remote memory in mice. PLoS ONE. 2008;3:e2121 pubmed publisher
    ..Secondary screens confirmed that mutations of integrin beta2 (Itgbeta2) and steryl-O-acyl transferase 1 (Soat1) specifically disrupted remote memory...
  8. Festenstein H, Berumen L. BALB.D2-Mlsa--a new congenic mouse strain. Transplantation. 1984;37:322-4 pubmed
  9. Uelmen P, Oka K, Sullivan M, Chang C, Chang T, Chan L. 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. 1995;270:26192-201 pubmed
    ..Two transfected Chinese hamster ovary cell lines that expressed the mouse ACAT transgene regained the ability to esterify cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) ..

More Information

Publications54

  1. Wilson C, Erdos E, Wilson J, Taylor B. Location on chromosome 1 of Rnr, a gene that regulates renin in the submaxillary gland of the mouse. Proc Natl Acad Sci U S A. 1978;75:5623-6 pubmed
    ..Documentation that a single gene can have major effects on renin in the submaxillary gland of the mouse implies that single gene differences might explain known variations in renin in other species. ..
  2. Freeman N, Rusinol A, Linton M, Hachey D, Fazio S, Sinensky M, et al. Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages. J Lipid Res. 2005;46:1933-43 pubmed
    ..These results suggest that 7KC not only initiates the apoptosis pathway by activating cPLA2, as we have reported previously, but also participates in the downstream signaling pathway when esterified by ACAT to form 7KC-arachidonate. ..
  3. Huang L, Melton E, Li H, Sohn P, Rogers M, Mulligan Kehoe M, et al. Myeloid Acyl-CoA:Cholesterol Acyltransferase 1 Deficiency Reduces Lesion Macrophage Content and Suppresses Atherosclerosis Progression. J Biol Chem. 2016;291:6232-44 pubmed publisher
    Acyl-CoA:cholesterol acyltransferase 1 (Acat1) converts cellular cholesterol to cholesteryl esters and is considered a drug target for treating atherosclerosis...
  4. Potter C, Kern M, Baybo M, Pruett N, Godwin A, Sundberg J, et al. Dysregulated expression of sterol O-acyltransferase 1 (Soat1) in the hair shaft of Hoxc13 null mice. Exp Mol Pathol. 2015;99:441-4 pubmed publisher
    The cholesterol-metabolizing enzyme sterol O-acetyltransferase (SOAT1) is implicated in an increasing number of biological and pathological processes in a number of organ systems, including the differentiation of the hair shaft...
  5. Elliott R, Barlow D, Hogan B. Linkage of genes for laminin B1 and B2 subunits on chromosome 1 in mouse. In Vitro Cell Dev Biol. 1985;21:477-84 pubmed
    ..4 +/- 3.2 cM distal to the Pep-3 locus. There is no evidence in the mouse for pseudogenes for these proteins. ..
  6. Nguyen T, Sawyer J, Kelley K, Davis M, Kent C, Rudel L. ACAT2 and ABCG5/G8 are both required for efficient cholesterol absorption in mice: evidence from thoracic lymph duct cannulation. J Lipid Res. 2012;53:1598-609 pubmed publisher
    ..The data indicate that handling of sterols by the intestine involves both G5G8 and ACAT2 but that an additional factor (possibly Niemann-Pick C1-like 1) may be key in determining absorption efficiency...
  7. Meiner V, Welch C, Cases S, Myers H, Sande E, Lusis A, et al. Adrenocortical lipid depletion gene (ald) in AKR mice is associated with an acyl-CoA:cholesterol acyltransferase (ACAT) mutation. J Biol Chem. 1998;273:1064-9 pubmed
    ald, a recessive allele in AKR inbred mice, is responsible for complete adrenocortical lipid depletion in postpubertal males, which appears to be androgen dependent...
  8. Lu Z, Yuan Z, Miyoshi T, Wang Q, Su Z, Chang C, et al. Identification of Soat1 as a quantitative trait locus gene on mouse chromosome 1 contributing to hyperlipidemia. PLoS ONE. 2011;6:e25344 pubmed publisher
    ..b>Soat1, encoding sterol o-acyltransferase 1, is a functional candidate gene located underneath the proximal linkage peak...
  9. Cases S, Novak S, Zheng Y, Myers H, Lear S, Sande E, et al. ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning, expression, and characterization. J Biol Chem. 1998;273:26755-64 pubmed
    ..Mouse tissue expression studies and the disruption of the mouse ACAT gene (Acact) have indicated that more than one ACAT exists in mammals and specifically that another enzyme is important in ..
  10. Cui D, Thorp E, Li Y, Wang N, Yvan Charvet L, Tall A, et al. Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells. J Leukoc Biol. 2007;82:1040-50 pubmed
    ..These findings have implications for macrophage physiology in both AC clearance and atherosclerotic plaque progression. ..
  11. Wu B, Potter C, Silva K, Liang Y, Reinholdt L, Alley L, et al. Mutations in sterol O-acyltransferase 1 (Soat1) result in hair interior defects in AKR/J mice. J Invest Dermatol. 2010;130:2666-8 pubmed publisher
  12. Shibuya Y, Chang C, Huang L, Bryleva E, Chang T. Inhibiting ACAT1/SOAT1 in microglia stimulates autophagy-mediated lysosomal proteolysis and increases Aβ1-42 clearance. J Neurosci. 2014;34:14484-501 pubmed publisher
    Acyl-CoA:cholesterol acyltransferase 1 (ACAT1) is a resident endoplasmic reticulum enzyme that prevents the buildup of cholesterol in membranes by converting it to cholesterol esters...
  13. Doering C, Shire J, Kessler S, Clayton R. Genetic and biochemical studies of the adrenal lipid depletion phenotype in mice. Biochem Genet. 1973;8:101-11 pubmed
  14. Xie C, Zhou Z, Li N, Bian Y, Wang Y, Wang L, et al. Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine. J Lipid Res. 2012;53:2092-101 pubmed
    ..This study demonstrates that NPC1L1 mediates cholesterol entering enterocytes through vesicular endocytosis and that ezetimibe blocks this step in vivo. ..
  15. Su Z, Wang X, Tsaih S, Zhang A, Cox A, Sheehan S, et al. Genetic basis of HDL variation in 129/SvImJ and C57BL/6J mice: importance of testing candidate genes in targeted mutant mice. J Lipid Res. 2009;50:116-25 pubmed publisher
    To evaluate the effect of genetic background on high-density lipoprotein cholesterol (HDL) levels in Soat1(-/-) mice, we backcrossed sterol O-acyltransferase 1 (Soat1)(-/-) mice, originally reported to have elevated HDL levels, to C57BL/..
  16. Arnesen K. Adrenocortical lipid depletion and leukemia in mice. Acta Pathol Microbiol Scand Suppl. 1974;Suppl 248:15-9 pubmed
  17. Masterson J, McNamee E, Jedlicka P, Fillon S, Ruybal J, Hosford L, et al. CCR3 Blockade Attenuates Eosinophilic Ileitis and Associated Remodeling. Am J Pathol. 2011;179:2302-14 pubmed publisher
    ..Cellularity of local mesenteric lymph nodes, including T- and B-lymphocytes, was also significantly reduced. Thus, eosinophils participate in intestinal remodeling, supporting eosinophils as a novel therapeutic target...
  18. Elliott R, Romejko C, Hohman C. Mapping the gene for LTW-4, a 26,000 molecular weight major protein of mouse liver and kidney. Mol Gen Genet. 1980;180:17-22 pubmed
    ..The gene order is Dip-1 Rnr - (Sas-1, ald) - Ltw-4 - Mls. The map distance between (Dip-1, Rnr) and Ltw-4 is estimated to be 12.2 +/- 4...
  19. Meiner V, Cases S, Myers H, Sande E, Bellosta S, Schambelan M, 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;93:14041-6 pubmed
    ..Disruption of the gene for ACAT (Acact) in mice resulted in decreased cholesterol esterification in ACAT-deficient fibroblasts and adrenal membranes, and ..
  20. Green S, Steinberg D, Quehenberger O. Cloning and expression in Xenopus oocytes of a mouse homologue of the human acylcoenzyme A: cholesterol acyltransferase and its potential role in metabolism of oxidized LDL. Biochem Biophys Res Commun. 1996;218:924-9 pubmed
    ..Injection of ACAT mRNA into oocytes induced specific binding of OxLDL. ACAT is expressed in mouse macrophages as a approximately 3.6 kB transcript and the expression is upregulated in human THP-1 cells treated with PMA. ..
  21. Shibuya Y, Niu Z, Bryleva E, Harris B, Murphy S, Kheirollah A, et al. Acyl-coenzyme A:cholesterol acyltransferase 1 blockage enhances autophagy in the neurons of triple transgenic Alzheimer's disease mouse and reduces human P301L-tau content at the presymptomatic stage. Neurobiol Aging. 2015;36:2248-2259 pubmed publisher
    ..using small molecule enzyme inhibitors or genetic inactivation of acyl-coenzyme A (Acyl-CoA):cholesterol acyltransferase 1 (ACAT1) diminished amyloidopathy and restored cognitive deficits...
  22. Wilcox F, Hirschhorn L, Taylor B, Womack J, Roderick T. Genetic variation in alkaline phosphatase of the house mouse (Mus musculus) with emphasis on a manganese-requiring isozyme. Biochem Genet. 1979;17:1093-107 pubmed
    ..6 +/- 2.9 cM from the M1s locus on the side distal to the centromere. Test-cross data show the following gene order and recombination percentages: Dip-1 19.0 +/- 3.8% Lp 7.4 +/- 2.2% Akp-1. ..
  23. Bryleva E, Rogers M, Chang C, Buen F, Harris B, Rousselet E, et al. ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD. Proc Natl Acad Sci U S A. 2010;107:3081-6 pubmed publisher
    ..Our study supports the potential of ACAT1 as a therapeutic target for treating certain forms of AD. ..
  24. Tavtigian S, Zabludoff S, Wold B. Cloning of mid-G1 serum response genes and identification of a subset regulated by conditional myc expression. Mol Biol Cell. 1994;5:375-88 pubmed
    ..This suggests that a myc driven progression from G0 may have novel properties with implications for its action in oncogenesis. ..
  25. Yang W, Bai Y, Xiong Y, Zhang J, Chen S, Zheng X, et al. Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism. Nature. 2016;531:651-5 pubmed publisher
    ..ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy. ..
  26. Rodriguez A, Ashen M, Chen E. ACAT1 deletion in murine macrophages associated with cytotoxicity and decreased expression of collagen type 3A1. Biochem Biophys Res Commun. 2005;331:61-8 pubmed
    ..02). Thus, ACAT1 KO macrophages show biochemical changes consistent with increased cytotoxicity and also a novel association with decreased expression of collagen type 3A1. ..
  27. Taylor B, Meier H. Mapping the adrenal lipid depletion gene of the AKR/J mouse strain. Genet Res. 1975;26:307-12 pubmed
  28. Molne K, Brabrand G. Spontaneous adrenocortical lipid depletion in mice. Relationship to general growth, degeneration of adrenal X zone, and maturation of seminiferous eptthelium. Acta Pathol Microbiol Scand. 1968;72:478-90 pubmed
  29. Dove D, Su Y, Swift L, Linton M, Fazio S. ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages. Atherosclerosis. 2006;186:267-74 pubmed
    ..This change in cholesterol homeostasis may contribute to the atherogenic potential of ACAT1(-/-) macrophages. ..
  30. Hai Q, Ritchey B, Robinet P, Alzayed A, Brubaker G, Zhang J, et al. Quantitative Trait Locus Mapping of Macrophage Cholesterol Metabolism and CRISPR/Cas9 Editing Implicate an ACAT1 Truncation as a Causal Modifier Variant. Arterioscler Thromb Vasc Biol. 2018;38:83-91 pubmed publisher
    ..This locus harbors the Soat1 (sterol O-acyltransferase 1) gene, encoding Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), which esterifies free cholesterol...
  31. Gessler M, Hameister H, Henry I, Junien C, Braun T, Arnold H. The human MyoD1 (MYF3) gene maps on the short arm of chromosome 11 but is not associated with the WAGR locus or the region for the Beckwith-Wiedemann syndrome. Hum Genet. 1990;86:135-8 pubmed
    ..5 related to the Beckwith-Wiedemann syndrome. Subregional mapping by in situ hybridization with an myf3 specific probe shows that the gene resides at the chromosomal band 11p14, possibly at 11p14.3. ..
  32. Rogers M, Liu J, Kushnir M, Bryleva E, Rockwood A, Meikle A, et al. Cellular pregnenolone esterification by acyl-CoA:cholesterol acyltransferase. J Biol Chem. 2012;287:17483-92 pubmed publisher
    ..Acyl-CoA:cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2) convert various sterols to steryl esters; their activities are activated by ..
  33. Meiner V, Tam C, Gunn M, Dong L, Weisgraber K, Novak S, et al. Tissue expression studies on the mouse acyl-CoA: cholesterol acyltransferase gene (Acact): findings supporting the existence of multiple cholesterol esterification enzymes in mice. J Lipid Res. 1997;38:1928-33 pubmed
    ..Although initial studies of the mouse acyl CoA:cholesterol acyltransferase gene (Acact) suggested that its gene product was responsible for cholesterol esterification in most tissues, we observed ..
  34. Szymura J, Taylor B, Klein J. Upg-2: a urinary pepsinogen variant located on chromosome 1 of the mouse. Biochem Genet. 1982;20:1211-9 pubmed
    ..Typing of recombinant inbred strains suggests that the location of the Upg-2 locus is on chromosome 1, in the vicinity of loci coding for other peptidases, namely, Pep-2 and Rnr, and of the Acf-1 locus. ..
  35. Welch C, Xia Y, Hong H, Stallcup M, Lusis A. Localization of the mouse glucocorticoid receptor-interacting protein 1 gene (Grip1) to proximal chromosome 1 by linkage analysis. Mamm Genome. 1997;8:620-1 pubmed
  36. Wu M, Cohen D. Altered hepatic cholesterol metabolism compensates for disruption of phosphatidylcholine transfer protein in mice. Am J Physiol Gastrointest Liver Physiol. 2005;289:G456-61 pubmed
    ..We speculate that regulation of cholesterol homeostasis is a physiological function of PC-TP in liver, which can be overcome with a cholesterol-rich lithogenic diet. ..
  37. Yamazaki K, Oki T, Tanaka I. Cloning of 5'-flanking region and a polymorphic CTT trinucleotide repeat within 5'-untranslated region of mouse R-type calcium channel alpha1-subunit (Cchra1) gene, and its genetic mapping. Gene. 1998;214:199-204 pubmed
    ..Using this polymorphism, the Cchra1 was mapped to the region of chromosome 1 where the synteny to human chromosome 1q was conserved. ..
  38. Frank D, Mendelsohn C, Ciccone E, Svensson K, Ohlsson R, Tycko B. A novel pleckstrin homology-related gene family defined by Ipl/Tssc3, TDAG51, and Tih1: tissue-specific expression, chromosomal location, and parental imprinting. Mamm Genome. 1999;10:1150-9 pubmed
    ..The data also define a new subfamily of PH domain genes. ..
  39. Giehl K, Potter C, Wu B, Silva K, Rowe L, Awgulewitsch A, et al. Hair interior defect in AKR/J mice. Clin Exp Dermatol. 2009;34:509-17 pubmed publisher
    ..This study sought to characterize the clinical and ultrastructural features of the hair interior defect (HID) phenotype and to determine the chromosomal localization of the hid mutant gene locus...
  40. Saadane A, Mast N, Dao T, Ahmad B, Pikuleva I. Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells. J Biol Chem. 2016;291:20427-39 pubmed publisher
  41. Burmeister M, Ren Q, Makris G, Samson D, Bennett V. Genes for the neuronal immunoglobulin domain cell adhesion molecules neurofascin and Nr-CAM map to mouse chromosomes 1 and 12 and homologous human chromosomes. Mamm Genome. 1996;7:558-9 pubmed
  42. Accad M, Smith S, Newland D, Sanan D, King L, Linton M, et al. Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1. J Clin Invest. 2000;105:711-9 pubmed
  43. Johnstone C, White S, Tebbutt N, Clay F, Ernst M, Biggs W, et al. Analysis of the regulation of the A33 antigen gene reveals intestine-specific mechanisms of gene expression. J Biol Chem. 2002;277:34531-9 pubmed
    ..Taken together, our data lead us to propose that the activity of CDX1 is pivotal in mediating the exquisite, intestine-specific expression pattern of the A33 antigen gene. ..
  44. Molne K. Autoradiographic studies on the incorporation of H-uridine into the adrenal glands of mice with spontaneous adrenocortical lipid depletion. A comparison with C57B1 mice. Acta Pathol Microbiol Scand. 1969;77:369-78 pubmed
  45. Arnesen K. Constitutional difference in lipid content of adrenals in two strains of mice and their hybrids. Acta Endocrinol (Copenh). 1955;18:396-401 pubmed