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.
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.
|Allele Name||targeted mutation 1, Rosalind Coleman|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Gpat1-; mtGPAT-|
|Gene Symbol and Name||Gpam, glycerol-3-phosphate acyltransferase, mitochondrial|
|Strain of Origin||129S6/SvEvTac|
|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.|
|Mutations Made By|| |
Rosalind Coleman, University of North Carolina
When maintaining a live colony, these mice are bred as homozygotes.
When using the mtGPAT- mouse strain in a publication, please cite the originating article(s) and include JAX stock #005429 in your Materials and Methods section.