Overview

Also Known As: TgSREBP-1a460

These TgSREBP-1a460 mice express a transgene containing the human sterol regulatory element binding transcription factor 1 (SREBF1) under control of the rat phosphoenolpyruvate carboxykinase (Pck1) promoter and develop a fatty liver.

Donating Investigator

Robert E Hammer, UT Southwestern Medical Center at Dallas

Genetic overview

Genetic Background	Generation

Tg(SREBP1a)7343Reh

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

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Research Applications

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The NH2-terminal domain of sterol-regulatory element binding protein-1a (SREBP-1a) activates transcription of genes encoding enzymes of cholesterol and fatty acid biosynthesis in cultured cells. These transgenic mice overexpress a truncated version of human SREBP-1a that includes the NH2-terminal domain but lacks the membrane attachment site. Expression is driven by the rat phosphoenolpyruvate carboxykinase (Pck1, also called Pepck) promoter, which gives high level expression in liver. When placed on a low carbohydrate/high protein diet to induce the Pck1 promoter the transgenic mice develop progressive and massive enlargement of the liver due to the engorgement of hepatocytes with cholesterol and triglycerides. The mRNAs encoding 3-hydroxy-3-methylglutaryl CoA (HMG CoA) synthase, HMG CoA reductase, squalene synthase, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1 are elevated, as is the LDL receptor mRNA. The rates of cholesterol and fatty acid synthesis in liver is elevated 5- and 25-fold, respectively. Plasma lipid levels are not elevated. The amount of white adipose tissue decreases progressively as the liver enlarges. (Shimano H, et al., J Clin Invest. 1996, 98:1575)

Expression Data

Expressed Gene	SREBF1, sterol regulatory element binding transcription factor 1, human
Site of Expression

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Shimano H; Horton JD; Hammer RE; Shimomura I; Brown MS; Goldstein JL. 1996. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a [see comments] J Clin Invest 98(7):1575-84PubMed: 8833906 MGI: J:35770

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Genetics

Tg(SREBP1a)7343Reh

Allele Symbol: Tg(SREBP1a)7343Reh

Allele Name	transgene insertion 7343, Robert E Hammer
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	transgene insertion 7343, Robert E Hammer; Tg(SREBP1a)7343Reh
Gene Symbol and Name	Tg(SREBP1a)7343Reh, transgene insertion 7343, Robert E Hammer
Gene Synonym(s)	S+; Tg(SREBF1)2Mbjg; TgSREBP-1a
Promoter	Pepck, Pck1-phosphoenolpyruvate carboxykinase,
Expressed Gene	SREBF1, sterol regulatory element binding transcription factor 1, human
Strain of Origin	Not Specified
Chromosome	UN
Molecular Note	The transgene contains human sterol regulatory element binding transcription factor 1 (SREBF1) under control of the phosphoenolpyruvate carboxykinase (Pck1) promoter. Seven lines were created.
Mutations Made By	Robert Hammer, UT Southwestern Medical Center at Dallas

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

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

Genotype: Tg(SREBP1a)7343Reh/0
B6.Cg-Tg(SREBP1a)7343Reh

adipose tissue phenotype

lipodystrophy
- lipodystrophy (loss and abnormal redistribution of body fat)

liver/biliary system phenotype

enlarged liver

mammalian phenotype

homeostasis/metabolism phenotype
- Normal - despite peripheral insulin resistance, mice exhibit normal non-esterified fatty acid levels in the plasma and do not develop diabetes

endocrine/exocrine gland phenotype

increased pancreatic beta cell mass
- beta cell mass is increased 3-fold compared to in wild-type mice

pancreatic islet hyperplasia

homeostasis/metabolism phenotype

decreased circulating leptin level

improved glucose tolerance

increased circulating glucose level
- fasting glucose levels are slightly higher than in wild-type mice

increased circulating insulin level
- mice exhibit postprandial hyperinsulinemia
- when fed ad libitum and following glucose loading, mice exhibit increased circulating insulin levels

insulin resistance
- mice exhibit peripheral insulin resistance

Genotype: Tg(SREBP1a)7343Reh/0
Not Specified

liver/biliary system phenotype

decreased liver regeneration
- after 70% resection, liver regeneration is suppressed due to decreased proliferation compared to in wild-type mice

Genotype: Tg(SREBP1a)7343Reh/?
involves: 129 * C57BL/6 * C57BL/6J * SJL

homeostasis/metabolism phenotype

decreased cholesterol level
- significant reduction in cholesterol in all lipoprotein fractions

decreased circulating cholesterol level
- decrease in total cholesterol in the plasma

decreased circulating HDL cholesterol level
- decrease in total cholesterol is largely the result of a decrease in HDL cholesterol

liver/biliary system phenotype

enlarged liver

mammalian phenotype

renal/urinary system phenotype
- Normal - unlike transgenic mice that are also null for Lcat, no significant ultrastructural kidney abnormalities are detected

renal/urinary system phenotype

abnormal renal glomerulus morphology
- occasional foci of mild arteriolar hyalinosis

expanded mesangial matrix
- focal mild mesangial matrix expansion

mesangial cell hyperplasia
- occasional foci of mild mesangial hypercellularity are seen

The following phenotype relates to a compound genotype created using this strain

Genotype: Tg(SREBP1a)7343Reh/0
involves: C57BL/6J * SJL/J

adipose tissue phenotype

abnormal fat pad morphology
- mice exhibit a decrease in subcutaneous, omental, perirenal and epididymal fat compared to in wild-type mice

decreased epididymal fat pad weight
- after being fed a low carbohydrate/high protein diet for 2 weeks, epididymal fat pad weight is decreased by more than 90% compared to similarly treated wild-type mice

liver/biliary system phenotype

abnormal hepatocyte morphology
- at 16 weeks of age mice exhibit distended hepatocytes due to fat droplet accumulation

enlarged liver
- after birth, mice exhibit abdominal swelling due to an enlarged liver than continues to enlarge after weaning when mice are placed on a low carbohydrate/high protein diet
- liver enlargement occurs due to increased lipid accumulation

increased liver cholesterol level
- after being fed a low carbohydrate/high protein diet for 2 weeks, liver cholesterol levels are increased 4.7-fold compared to in wild-type mice
- Normal - however, plasma cholesterol levels are normal

increased liver triglyceride level
- after being fed a low carbohydrate/high protein diet for 2 weeks, liver triglyceride levels are increased 21-fold compared to in wild-type mice

increased liver weight
- after being fed a low carbohydrate/high protein diet for 2 weeks, liver weight is increased 4-fold compared to similarly treated wild-type mice

pale liver

mammalian phenotype

homeostasis/metabolism phenotype
- Normal - despite increases in liver lipid synthesis and content after being fed a low carbohydrate/high protein diet for 2 weeks, mice exhibit normal plasma glucose, creatinine, alkaline phophatase, bilirubin, and blood urea nitrogen levels

liver/biliary system phenotype
- Normal - despite accumulation of fat in the liver, mice do not exhibit generalized inflammation in the liver or liver necrosis

homeostasis/metabolism phenotype

abnormal lipid homeostasis
- lipid biosynthesis is increased compared to in wild-type mice

decreased circulating triglyceride level
- modest

increased circulating aspartate transaminase level

increased circulating serum albumin level

increased circulating total protein level

increased liver cholesterol level
- after being fed a low carbohydrate/high protein diet for 2 weeks, liver cholesterol levels are increased 4.7-fold compared to in wild-type mice
- Normal - however, plasma cholesterol levels are normal

increased liver triglyceride level
- after being fed a low carbohydrate/high protein diet for 2 weeks, liver triglyceride levels are increased 21-fold compared to in wild-type mice

References

Shimano H; Horton JD; Hammer RE; Shimomura I; Brown MS; Goldstein JL. 1996. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a [see comments] J Clin Invest 98(7):1575-84PubMed: 8833906 MGI: J:35770

Additional - Tg(SREBP1a)7343Reh related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Tg(SREBP1a)7343Reh
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, hemizygous mice may be bred to wildtype siblings, or to B6SJLF1/J mice (Stock No. 10012).
- Additional Breeding and Husbandry Support
Appearance
- multiple coat colors
  Related Genotype: a, A, Oca2^p, Tyr^c and Pde6b^rd1
Citation
When using the TgSREBP-1a460 mouse strain in a publication, please cite the originating article(s) and include JAX stock #002840 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(SREBP1a)7343Reh

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

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"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "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 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, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

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In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

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The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

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Also Known As: TgSREBP-1a460

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(SREBP1a)7343Reh

Allele Symbol: Tg(SREBP1a)7343Reh

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(SREBP1a)7343Reh/0B6.Cg-Tg(SREBP1a)7343Reh

adipose tissue phenotype

liver/biliary system phenotype

mammalian phenotype

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

Genotype: Tg(SREBP1a)7343Reh/0Not Specified

liver/biliary system phenotype

Genotype: Tg(SREBP1a)7343Reh/?involves: 129 * C57BL/6 * C57BL/6J * SJL

homeostasis/metabolism phenotype

liver/biliary system phenotype

mammalian phenotype

renal/urinary system phenotype

Genotype: Tg(SREBP1a)7343Reh/0involves: C57BL/6J * SJL/J

adipose tissue phenotype

liver/biliary system phenotype

mammalian phenotype

homeostasis/metabolism phenotype

References

Additional - Tg(SREBP1a)7343Reh related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(SREBP1a)7343Reh/0
B6.Cg-Tg(SREBP1a)7343Reh

Genotype: Tg(SREBP1a)7343Reh/0
Not Specified

Genotype: Tg(SREBP1a)7343Reh/?
involves: 129 * C57BL/6 * C57BL/6J * SJL

Genotype: Tg(SREBP1a)7343Reh/0
involves: C57BL/6J * SJL/J