Former Names B6;129-Scaptm1Gsn/J (Changed: 04-MAY-06 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Dr. Jay D. Horton, Univ of Texas SW Med Center at Dallas
Mice that are homozygous for this targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. They posses a loxP-flanked neomycin resistance cassette located 3 kb upstream of exon 1. A third loxP site is located in intron 1. When used in conjunction with a Cre recombinase-expressing strain, this strain is appropriate for generating tissue-specific knockout mutants of Scap. This mutant mouse strain represents a model that may be useful in studies related to cholesterol and fatty acid homeostasis.
A targeting vector containing a loxP-flanked neo cassette located 3kb 5' of Scap exon 1 and a third loxP site located in intron 1, was electroporated into 129S6/SvEv-derived SM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were mated to C57BL/6 mice.
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|Allele Name||targeted mutation 1, Joseph L Goldstein|
|Allele Type||Targeted (Floxed/Frt)|
|Common Name(s)||SCAPflox; Scap-; Scaptm1Gsn;|
|Mutation Made By||Dr. Jay Horton, Univ of Texas SW Med Center at Dallas|
|Strain of Origin||129S6/SvEvTac|
|ES Cell Line Name||SM1|
|ES Cell Line Strain||129S6/SvEvTac|
|Gene Symbol and Name||Scap, SREBF chaperone|
|Molecular Note||A a loxP-flanked neomycin resistance cassette located 3 kb upstream of exon 1. An additional loxP site was inserted in intron 1. [MGI Ref ID J:69592]|
Matsuda M; Korn BS; Hammer RE; Moon YA; Komuro R; Horton JD; Goldstein JL; Brown MS; Shimomura I. 2001. SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. Genes Dev 15(10):1206-16. [PubMed: 11358865] [MGI Ref ID J:69592]
Besnard V; Wert SE; Stahlman MT; Postle AD; Xu Y; Ikegami M; Whitsett JA. 2009. Deletion of Scap in alveolar type II cells influences lung lipid homeostasis and identifies a compensatory role for pulmonary lipofibroblasts. J Biol Chem 284(6):4018-30. [PubMed: 19074148] [MGI Ref ID J:147592]
Horton JD; Shah NA; Warrington JA; Anderson NN; Park SW; Brown MS; Goldstein JL. 2003. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A 100(21):12027-32. [PubMed: 14512514] [MGI Ref ID J:86192]
Kuriyama H; Liang G; Engelking LJ; Horton JD; Goldstein JL; Brown MS. 2005. Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver. Cell Metab 1(1):41-51. [PubMed: 16054043] [MGI Ref ID J:129815]
Li J; Nanayakkara A; Jun J; Savransky V; Polotsky VY. 2007. Effect of deficiency in SREBP cleavage-activating protein on lipid metabolism during intermittent hypoxia. Physiol Genomics 31(2):273-80. [PubMed: 17666524] [MGI Ref ID J:128622]
Moon YA; Liang G; Xie X; Frank-Kamenetsky M; Fitzgerald K; Koteliansky V; Brown MS; Goldstein JL; Horton JD. 2012. The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell Metab 15(2):240-6. [PubMed: 22326225] [MGI Ref ID J:182284]
Rudolph MC; Monks J; Burns V; Phistry M; Marians R; Foote MR; Bauman DE; Anderson SM; Neville MC. 2010. Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epithelium. Am J Physiol Endocrinol Metab 299(6):E918-27. [PubMed: 20739508] [MGI Ref ID J:170224]
Verdier V; Csardi G; de Preux-Charles AS; Medard JJ; Smit AB; Verheijen MH; Bergmann S; Chrast R. 2012. Aging of myelinating glial cells predominantly affects lipid metabolism and immune response pathways. Glia 60(5):751-60. [PubMed: 22337502] [MGI Ref ID J:181551]
Verheijen MH; Camargo N; Verdier V; Nadra K; de Preux Charles AS; Medard JJ; Luoma A; Crowther M; Inouye H; Shimano H; Chen S; Brouwers JF; Helms JB; Feltri ML; Wrabetz L; Kirschner D; Chrast R; Smit AB. 2009. SCAP is required for timely and proper myelin membrane synthesis. Proc Natl Acad Sci U S A 106(50):21383-8. [PubMed: 19948958] [MGI Ref ID J:155526]
Breeding & Husbandry This strain originated on a B6;129S6 background. It is maintained as a homozygote on the same background. Diet Information LabDiet® 5K52/5K67
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