Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Rosalind Coleman,   University of North Carolina

Description
Mice that are homozygous for the targeted mutation are viable, fertile, and do not display any gross behavioral abnormalities. No gene product (mRNA) is detected by Northern blot analysis. Enzyme activity levels in liver tissue are negligible. Residual activity is due to the inactivated microsomal isoform. Homozygotes exhibit reduced body weight. Female homozygotes weigh 20% less than wildtype controls at age 10 months. Male homozygotes do not exhibit as significant a weight reduction. Gonadal fat pad mass is reduced. Liver triacylglycerol and plasma lipid levels are reduced by 37% and 15% respectively. Very low density lipoprotein (VLDL) triacylglycerol level and secretion are decreased. Hepatic triacylglycerol fatty acid and phospholipid fatty acid compositions are abnormal with diminished palmitate content. F2 mice on a 50% C57BL/6J and 50% 129SvEv genetic background were used in all of the experiments described in the primary reference. This mutant mouse strain may be useful in studies of fatty acid metabolism, lipid homeostasis and triacylglycerol and phospholipid synthesis regulation.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 0.5kb of sequence encoding 62 amino acids in homology regions II and III. The construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric male animals were crossed to C57BL/6J female mice, and then backcrossed to the same for 6 generations.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Gpam^tm1Rcol/Gpam^tm1Rcol

        involves: 129S6/SvEvTac * C57BL/6J

• adipose tissue phenotype
• abnormal gonadal fat pad morphology (MGI Ref ID J:84541)
  • reduced gonadal fat pad weight
• growth/size phenotype
• decreased body weight (MGI Ref ID J:84541)
• homeostasis/metabolism phenotype
• abnormal fatty acid level (MGI Ref ID J:84541)
  • altered glycerolipid fatty acid composition
• decreased triglyceride level (MGI Ref ID J:84541)
  • reduced hepatic triglyceride levels
• decreased circulating triglyceride level (MGI Ref ID J:84541)

View Research Applications

Research Applications

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

Cardiovascular Research
Other (altered lipoprotein profile)

Internal/Organ Research
Adipose Defects

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information

Allele Symbol		Gpamtm1Rcol
Allele Name		targeted mutation 1, Rosalind Coleman
Allele Type		Targeted (knock-out)
Common Name(s)		Gpat1-; mtGPAT-;
Mutation Made By		Rosalind Coleman,   University of North Carolina
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Gpam, glycerol-3-phosphate acyltransferase, mitochondrial
Chromosome		19
Gene Common Name(s)		GPAT1; KIAA1560; MGC26846; RP11-426E5.2;
Molecular Note		A 0.5 kb genomic fragment encoding 62 amino acids including those that make up homology regions II and III was replaced with a neo cassette inserted by homologous recombination. Transcript was undetected by Northern blot analysis of homozygous mutant liver tissue. Activity assays indicated a near comlpete ablation of endogenous activity and showed that the activity of the microsomal isoform was unperturbed. [MGI Ref ID J:84541]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Hammond LE; Gallagher PA; Wang S; Hiller S; Kluckman KD; Posey-Marcos EL; Maeda N; Coleman RA. 2002. Mitochondrial glycerol-3-phosphate acyltransferase-deficient mice have reduced weight and liver triacylglycerol content and altered glycerolipid fatty acid composition. Mol Cell Biol 22(23):8204-14. [PubMed: 12417724]  [MGI Ref ID J:84541]

Additional References

Gpam^tm1Rcol related

Gonzalez-Baro MR; Lewin TM; Coleman RA. 2007. Regulation of Triglyceride Metabolism. II. Function of mitochondrial GPAT1 in the regulation of triacylglycerol biosynthesis and insulin action. Am J Physiol Gastrointest Liver Physiol 292(5):G1195-9. [PubMed: 17158253]  [MGI Ref ID J:122621]

Hammond LE; Neschen S; Romanelli AJ; Cline GW; Ilkayeva OR; Shulman GI; Muoio DM; Coleman RA. 2005. Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential in liver for the metabolism of excess acyl-CoAs. J Biol Chem 280(27):25629-36. [PubMed: 15878874]  [MGI Ref ID J:106957]

Lewin TM; Schwerbrock NM; Lee DP; Coleman RA. 2004. Identification of a new glycerol-3-phosphate acyltransferase isoenzyme, mtGPAT2, in mitochondria. J Biol Chem 279(14):13488-95. [PubMed: 14724270]  [MGI Ref ID J:89170]

Lewin TM; de Jong H; Schwerbrock NJ; Hammond LE; Watkins SM; Combs TP; Coleman RA. 2008. Mice deficient in mitochondrial glycerol-3-phosphate acyltransferase-1 have diminished myocardial triacylglycerol accumulation during lipogenic diet and altered phospholipid fatty acid composition. Biochim Biophys Acta 1781(6-7):352-8. [PubMed: 18522808]  [MGI Ref ID J:137056]

Neschen S; Morino K; Hammond LE; Zhang D; Liu ZX; Romanelli AJ; Cline GW; Pongratz RL; Zhang XM; Choi CS; Coleman RA; Shulman GI. 2005. Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice. Cell Metab 2(1):55-65. [PubMed: 16054099]  [MGI Ref ID J:129839]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
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

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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