Strain Name:

B6.129S4-Soat2tm1Far/J

Stock Number:

004185

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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

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Robert V Farese, Jr.,   Gladstone Institute UCSF

Description
Mice that are homozygous null for this targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Southern blot analysis and RT-PCR indicated the targeted gene was disrupted. These mice lack cholesterol ester synthesis in liver and intestine and are resistant to diet-induced hypercholesterolemia and cholesterol gallstone formation. In homozygous mice fed regular diet, acyl CoA: cholesterol acyltransferase (ACAT) enzyme activity was reduced by 92% in intestine, and by 99% in liver. Homozygous mice fed high-fat/high cholesterol diet had low ACAT activity. Although ACAT2 deficient mice absorb less cholesterol than wild-type mice when fed a high fat/ high cholesterol diet, histological examination indicated enterocytes in the mutant mice were normal. This mutant mouse strain represents a model that may be useful in studies related to human resistance to diet-induced hypercholesterolemia and cholesterol gallstone formation.

Development
A targeting vector containing approximately 1.5 kb Soat2 sequence, neomycin resistance, and herpes simplex virus thymidine kinase genes was utilized in the construction of this mutant. The Soat2 sequence targeted in the construct corresponded to the carboxy terminal and 28% of the ACAT2 protein. The construct was electroporated into 129S4/SvJae derived RF8 embryonic stem (ES) cells. Selected ES cells were then used to generate mice.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Soat2tm1Far/Soat2tm1Far

        involves: 129S4/SvJae * C57BL/6J
  • homeostasis/metabolism phenotype
  • abnormal cholesterol homeostasis
    • reduction in cholesterol ester synthesis in the small intestine and liver   (MGI Ref ID J:82032)
    • decreased circulating cholesterol level
      • homozygotes exhibit resistance to diet-induced hypercholesterolemia; cholesterol in the VLDL, LDL and IDL fractions is reduced   (MGI Ref ID J:82032)
      • decreased circulating LDL cholesterol level
        • homozygotes fed a high-fat (7.5%), high-cholesterol (1.25%) and 0.5% cholic acid diet exhibit reduced cholesterol in the LDL fraction compared to wild-type   (MGI Ref ID J:82032)
      • decreased circulating VLDL cholesterol level
        • homozygotes fed a high-fat (7.5%), high-cholesterol (1.25%) and 0.5% cholic acid diet exhibit reduced cholesterol in the VLDL fraction compared to wild-type   (MGI Ref ID J:82032)
    • increased circulating HDL cholesterol level
      • mutants fed a western diet (20% fat and 0.15% cholesterol) exhibit increases in plasma HDL cholesterol   (MGI Ref ID J:82032)
  • decreased intestinal cholesterol absorption
    • cholesterol absorption in homozygotes fed a high-fat (7.5%), high-cholesterol (1.25%) and 0.5% cholic acid diet is 85% lower than in wild-type   (MGI Ref ID J:82032)
  • increased circulating triglyceride level
    • homozygotes fed a high-fat (7.5%), high-cholesterol (1.25%) and 0.5% cholic acid diet or a chow diet exhibit elevated serum triglyceride level compared to wild-type fed the same diet; VLDL, IDL, and LDL fractions are increased   (MGI Ref ID J:82032)
  • liver/biliary system phenotype
  • abnormal gallbladder physiology
    • homozygotes exhibit resistance to diet-induced cholesterol gallstone formation   (MGI Ref ID J:82032)
    • abnormal bile composition
      • mutants on a high-fat (7.5%), high-cholesterol (1.25%) and 0.5% cholic acid diet exhibit bile cholesterol concentrations that are 30% lower than in wild-type mice   (MGI Ref ID J:82032)
  • decreased susceptibility to hepatic steatosis
    • when fed a high-fat (7.5%), high-cholesterol (1.25%) and 0.5% cholic acid diet, mutants do not develop fat-laden livers as seen in wild-type mice on the same diet   (MGI Ref ID J:82032)
  • digestive/alimentary phenotype
  • abnormal small intestine morphology
    • free cholesterol levels are increased by 30% in the small intestine of mutants fed a high-fat (7.5%), high-cholesterol (1.25%) and 0.5% cholic acid diet   (MGI Ref ID J:82032)
  • decreased intestinal cholesterol absorption
    • cholesterol absorption in homozygotes fed a high-fat (7.5%), high-cholesterol (1.25%) and 0.5% cholic acid diet is 85% lower than in wild-type   (MGI Ref ID J:82032)
View Research Applications

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

Soat2tm1Far related

Cardiovascular Research
Hypercholesterolemia
      Resistant

Metabolism Research
Lipid Metabolism

Research Tools
Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Soat2tm1Far
Allele Name targeted mutation 1, Bob Farese
Allele Type Targeted (knock-out)
Common Name(s) ACAT2;
Mutation Made By Robert Farese, Jr.,   Gladstone Institute UCSF
Strain of Origin129S4/SvJae
ES Cell Line NameRF8
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Soat2, sterol O-acyltransferase 2
Chromosome 15
Gene Common Name(s) ACACT2; ACAT2; ARGP2; Acat-2; D15Wsu97e; DNA segment, Chr 15, Wayne State University 97, expressed;
Molecular Note The gene was disrupted by replacement of 1.5 kb of 3' sequences with a neomycin resistance cassette by homologous recombination. The gene targeting event results in deletion of 28% of the protein coding sequence. Absence of gene expression in homozygous mutant animals was confirmed by RT-PCR analysis of mRNA from liver and small intestines. [MGI Ref ID J:82032]

Genotyping

Genotyping Information

Genotyping Protocols

Soat2tm1Far,

Separated MCA


Generic Neo Melt Curve Analysis, Melt Curve Analysis
Soat2tm1Far, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Buhman KK; Accad M; Novak S; Choi RS; Wong JS; Hamilton RL; Turley S; Farese RV Jr. 2000. Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat Med 6(12):1341-7. [PubMed: 11100118]  [MGI Ref ID J:82032]

Additional References

Soat2tm1Far related

Alger HM; Brown JM; Sawyer JK; Kelley KL; Shah R; Wilson MD; Willingham MC; Rudel LL. 2010. Inhibition of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) prevents dietary cholesterol-associated steatosis by enhancing hepatic triglyceride mobilization. J Biol Chem 285(19):14267-74. [PubMed: 20231283]  [MGI Ref ID J:162960]

Bell TA 3rd; Kelley K; Wilson MD; Sawyer JK; Rudel LL. 2007. Dietary fat-induced alterations in atherosclerosis are abolished by ACAT2-deficiency in ApoB100 only, LDLr-/- mice. Arterioscler Thromb Vasc Biol 27(6):1396-402. [PubMed: 17431188]  [MGI Ref ID J:134910]

Brown JM; Bell TA 3rd; Alger HM; Sawyer JK; Smith TL; Kelley K; Shah R; Wilson MD; Davis MA; Lee RG; Graham MJ; Crooke RM; Rudel LL. 2008. Targeted depletion of hepatic ACAT2-driven cholesterol esterification reveals a non-biliary route for fecal neutral sterol loss. J Biol Chem 283(16):10522-34. [PubMed: 18281279]  [MGI Ref ID J:136556]

Bryleva EY; Rogers MA; Chang CC; Buen F; Harris BT; Rousselet E; Seidah NG; Oddo S; LaFerla FM; Spencer TA; Hickey WF; Chang TY. 2010. 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 107(7):3081-6. [PubMed: 20133765]  [MGI Ref ID J:157545]

Lee RG; Kelley KL; Sawyer JK; Farese RV Jr; Parks JS; Rudel LL. 2004. Plasma cholesteryl esters provided by lecithin:cholesterol acyltransferase and acyl-coenzyme a:cholesterol acyltransferase 2 have opposite atherosclerotic potential. Circ Res 95(10):998-1004. [PubMed: 15486318]  [MGI Ref ID J:103854]

Lee RG; Shah R; Sawyer JK; Hamilton RL; Parks JS; Rudel LL. 2005. ACAT2 contributes cholesteryl esters to newly secreted VLDL, whereas LCAT adds cholesteryl ester to LDL in mice. J Lipid Res 46(6):1205-12. [PubMed: 15805543]  [MGI Ref ID J:128885]

Melchior JT; Sawyer JK; Kelley KL; Shah R; Wilson MD; Hantgan RR; Rudel LL. 2013. LDL particle core enrichment in cholesteryl oleate increases proteoglycan binding and promotes atherosclerosis. J Lipid Res 54(9):2495-503. [PubMed: 23804810]  [MGI Ref ID J:200774]

Nguyen TM; Sawyer JK; Kelley KL; Davis MA; Kent CR; Rudel LL. 2012. ACAT2 and ABCG5/G8 are both required for efficient cholesterol absorption in mice: evidence from thoracic lymph duct cannulation. J Lipid Res 53(8):1598-609. [PubMed: 22669916]  [MGI Ref ID J:186555]

Repa JJ; Buhman KK; Farese RV Jr; Dietschy JM; Turley SD. 2004. ACAT2 deficiency limits cholesterol absorption in the cholesterol-fed mouse: impact on hepatic cholesterol homeostasis. Hepatology 40(5):1088-97. [PubMed: 15486928]  [MGI Ref ID J:166503]

Rogers MA; Liu J; Kushnir MM; Bryleva E; Rockwood AL; Meikle AW; Shapiro D; Vaisman BL; Remaley AT; Chang CC; Chang TY. 2012. Cellular pregnenolone esterification by acyl-CoA:cholesterol acyltransferase. J Biol Chem 287(21):17483-92. [PubMed: 22474282]  [MGI Ref ID J:185622]

Temel RE; Lee RG; Kelley KL; Davis MA; Shah R; Sawyer JK; Wilson MD; Rudel LL. 2005. Intestinal cholesterol absorption is substantially reduced in mice deficient in both ABCA1 and ACAT2. J Lipid Res 46(11):2423-31. [PubMed: 16150828]  [MGI Ref ID J:104775]

Turley SD; Valasek MA; Repa JJ; Dietschy JM. 2010. Multiple mechanisms limit the accumulation of unesterified cholesterol in the small intestine of mice deficient in both ACAT2 and ABCA1. Am J Physiol Gastrointest Liver Physiol 299(5):G1012-22. [PubMed: 20724527]  [MGI Ref ID J:165824]

Willner EL; Tow B; Buhman KK; Wilson M; Sanan DA; Rudel LL; Farese RV Jr. 2003. Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc Natl Acad Sci U S A 100(3):1262-7. [PubMed: 12538880]  [MGI Ref ID J:81836]

Xie C; Zhou ZS; Li N; Bian Y; Wang YJ; Wang LJ; Li BL; Song BL. 2012. Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine. J Lipid Res 53(10):2092-2101. [PubMed: 22811412]  [MGI Ref ID J:188044]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryCoat color expected from breeding:Black

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2450.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $1600.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. 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.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 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).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3185.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $2080.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. 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.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 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).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  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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