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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
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
Former Names B6;129S6-Srebf1tm1Jdh (Changed: 15-DEC-04 ) 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 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 (255 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
- increase in the level of triglyceride in kedney with high fat diet seen in the control mice were prevented in mutant mice (MGI Ref ID J:101307)
- decreased circulating triglyceride level
- the level of plasma triglyceride was significantly reduced in 12 weeks old mice on normal diet (MGI Ref ID J:101307)
- decreased circulating cholesterol level
- the level of plasma cholesterol was significantly reduced in 12 weeks old mice on normal diet (MGI Ref ID J:101307)
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
- the level of plasma cholesterol was significantly reduced in 8-10 weeks old male mice on normal diet (MGI Ref ID J:75320)
- decreased circulating triglyceride level
- the level of plasma triglyceride was significantly reduced in 8-10 weeks old male mice on normal diet (MGI Ref ID J:75320)
- increased liver cholesterol level
- the liver cholesterol content was significantly increased in 8-10 weeks old male mice on normal diet (MGI Ref ID J:75320)
- liver/biliary system phenotype
- increased liver cholesterol level
- the liver cholesterol content was significantly increased in 8-10 weeks old male mice on normal diet (MGI Ref ID J:75320)
Srebf1tm1Mbr/Srebf1tm1Mbr
129S6(B6)-Srebf1tm1Mbr
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype
This mouse can be used to support research in many areas including:
Srebf1tm1Mbr relatedCardiovascular Research
Other
altered fat metabolism
altered lipoprotein profile
Metabolism Research
Lipid Metabolism
Research Tools
lacZ Expression
Cardiovascular Research
Metabolism Research
Metabolism Research
Lipid Metabolism
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Srebf1tm1Mbr | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Michael S Brown | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | SREBP-1c -; SREBP-1c null; | ||
| 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 | ||
| Site of Expression | Liver | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| 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] | ||
| Gene Symbol and Name | Srebf1, sterol regulatory element binding transcription factor 1 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | ADD-1; ADD1; SREBP-1; SREBP-1a; SREBP-1c; SREBP1; SREBP1c; bHLHd1; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Srebf1tm1Mbralternate1 MCA,Separated MCA
Srebf1tm1Mbr, Separated PCR
Srebf1tm1Mbralternate1, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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]
Pashkov V; Huang J; Parameswara VK; Kedzierski W; Kurrasch DM; Tall GG; Esser V; Gerard RD; Uyeda K; Towle HC; Wilkie TM. 2011. Regulator of G Protein Signaling (RGS16) Inhibits Hepatic Fatty Acid Oxidation in a Carbohydrate Response Element-binding Protein (ChREBP)-dependent Manner. J Biol Chem 286(17):15116-25. [PubMed: 21357625] [MGI Ref ID J:172091]
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]
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 & Husbandry This strain originated on a B6;129S6 background and is maintained as a homozygote. Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 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.
Embryos
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 |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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.
Embryos
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).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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For Licensing and Use Restrictions view the link(s) below:
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General inquiries regarding Terms of UseContracts Administration
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JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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