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- Description
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Description
Strain Information
Former Names B6;129S6-Srebf1tm1Jdh (Changed: 15-DEC-04 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Jay Horton, Univ of Texas SW Med Center at Dallas Description
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. The targeted mutation results in a total ablation of the SREBP-1c transcript and only a slight redution in levels of the alternate SREBP-1a transcript. There is a 50% increase in level of SREBP-2 transcript and increases in transcripts of enzymes utilized in cholesterol biosynthesis. Liver cholesterol content is increased while plasma cholesterol and plasma triglycerides levels are reduced. There is a reduction of expression of all genes required for fatty acid and triglyceride synthesis. Administration of liver X receptor (LXR) agonist did not result in increased levels of SREBP-1a transcript or in liver triglycerides. This mutant mouse strain represents a model that may be useful in studies of transcriptional control of fatty acid and triglyceride biosynthesis.Development
A targeting vector containing two copies of the herpes simplex virus thymidine kinase gene, a modified bacterial lacZ gene with a nuclear localization signal and the ACN cassette was used to disrupt the first exon and a portion of the promoter for the SREBP-1c isoform. The ACN cassette, containing the neomycin resistance gene and Cre recombinase gene under the control of angiotensin-converting enzyme promoter, is flanked by loxP sites. Cre-mediated recombination during spermatogenesis removed the cassette leaving one loxP site and resulted in lacZ gene expression controlled by the endogenous SREBP-1c promoter. The construct was electroporated into 129S6/SvEv derived SM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to B6;129S6 mice.
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (176 strains)
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Srebf1tm1Mbr/Srebf1tm1Mbr
involves: 129S6/SvEvTac * C57BL/6J
- homeostasis/metabolism phenotype
- abnormal triglyceride level (MGI Ref ID J:101307)
- increase in the level of triglyceride in kedney with high fat diet seen in the control mice were prevented in mutant mice
- decreased circulating triglyceride level (MGI Ref ID J:101307)
- the level of plasma triglyceride was significantly reduced in 12 weeks old mice on normal diet
- decreased circulating cholesterol level (MGI Ref ID J:101307)
- the level of plasma cholesterol was significantly reduced in 12 weeks old mice on normal diet
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Srebf1tm1Mbr/Srebf1tm1Mbr
involves: 129S6/SvEvTac
- homeostasis/metabolism phenotype
- decreased circulating cholesterol level (MGI Ref ID J:75320)
- the level of plasma cholesterol was significantly reduced in 8-10 weeks old male mice on normal diet
- decreased circulating triglyceride level (MGI Ref ID J:75320)
- the level of plasma triglyceride was significantly reduced in 8-10 weeks old male mice on normal diet
- increased cholesterol level (MGI Ref ID J:75320)
- the liver cholesterol content was significantly increased in 8-10 weeks old male mice on normal diet
Srebf1tm1Mbr/Srebf1tm1Mbr
129S6(B6)-Srebf1tm1Mbr
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype (MGI Ref ID J:111873)
- leptin treatment decreased body weight and food intake to the same extent in mutant mice as in the cortol
- leptin treatment decreased SCD1 activity to the same degree as seen in wild-type mice
This mouse can be used to support research in many areas including:
Srebf1tm1Mbr relatedCardiovascular Research
Other (altered fat metabolism)
Other (altered lipoprotein profile)
Metabolism Research
Lipid Metabolism
Research Tools
lacZ Expression
Cardiovascular Research
Metabolism Research
Metabolism Research
Lipid Metabolism
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Srebf1tm1Mbr | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Michael S Brown | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | SREBP-1c -; | ||
| Mutation Made By | 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 | ||
| Site of Expression | Liver | ||
| Gene Symbol and Name | Srebf1, sterol regulatory element binding transcription factor 1 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | ADD-1; SREBP-1; SREBP-1a; SREBP-1c; SREBP1; SREBP1c; bHLHd1; | ||
| Molecular Note | An in-frame lacZ gene with a nuclear localization signal was inserted into exon 1c of the gene. A loxP flanked neomycin resistance and Angiotensin-cre cassette (ACN) was inserted following the lacZ gene. The neomycin/cre cassette was autocatalytically removed in the male germline by activation of the Ace promoter in testis. RNase protection assays on liver RNA from homozygous mice demonstrated that the 1c isoform transcript was not detectable, while expression of the 1a isoform was unaffected. Western blot analysis confirmed that the expression of the encoded protein was greatly reduced from this allele; in addition, beta-galactosidase expression was detected from this allele in frozen liver sections. [MGI Ref ID J:75320] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Srebf1tm1Mbr, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Liang G; Yang J; Horton JD; Hammer RE; Goldstein JL; Brown MS. 2002. Diminished Hepatic Response to Fasting/Refeeding and Liver X Receptor Agonists in Mice with Selective Deficiency of Sterol Regulatory Element-binding Protein-1c. J Biol Chem 277(11):9520-8. [PubMed: 11782483] [MGI Ref ID J:75320]
Additional References
Miyazaki M; Dobrzyn A; Man WC; Chu K; Sampath H; Kim HJ; Ntambi JM. 2004. Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J Biol Chem 279(24):25164-71. [PubMed: 15066988] [MGI Ref ID J:90732]
Repa JJ; Liang G; Ou J; Bashmakov Y; Lobaccaro JM; Shimomura I; Shan B; Brown MS; Goldstein JL; Mangelsdorf DJ. 2000. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta Genes Dev 14(22):2819-30. [PubMed: 11090130] [MGI Ref ID J:65994]
Shimomura I; Hammer RE; Richardson JA; Ikemoto S; Bashmakov Y; Goldstein JL; Brown MS. 1998. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev 12(20):3182-94. [PubMed: 9784493] [MGI Ref ID J:50770]
Srebf1tm1Mbr relatedBiddinger SB; Miyazaki M; Boucher J; Ntambi JM; Kahn CR. 2006. Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element-binding protein-1c. Diabetes 55(7):2032-41. [PubMed: 16804073] [MGI Ref ID J:111873]
Chu K; Miyazaki M; Man WC; Ntambi JM. 2006. Stearoyl-coenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation. Mol Cell Biol 26(18):6786-98. [PubMed: 16943421] [MGI Ref ID J:112300]
Jiang T; Wang Z; Proctor G; Moskowitz S; Liebman SE; Rogers T; Lucia MS; Li J; Levi M. 2005. Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. J Biol Chem 280(37):32317-25. [PubMed: 16046411] [MGI Ref ID J:101307]
Kalaany NY; Gauthier KC; Zavacki AM; Mammen PP; Kitazume T; Peterson JA; Horton JD; Garry DJ; Bianco AC; Mangelsdorf DJ. 2005. LXRs regulate the balance between fat storage and oxidation. Cell Metab 1(4):231-44. [PubMed: 16054068] [MGI Ref ID J:129844]
Miyazaki M; Dobrzyn A; Man WC; Chu K; Sampath H; Kim HJ; Ntambi JM. 2004. Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J Biol Chem 279(24):25164-71. [PubMed: 15066988] [MGI Ref ID J:90732]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry This strain originated on a B6;129S6 background and is maintained as a homozygote. Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
Additional Supply Details
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| None Available | ||
| 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. | ||
General Terms and Conditions
See Terms of Use
The Jackson Laboratory's Genotype Promise
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