| Status | Available to order |
| EMMA ID | EM:05573 |
| International strain name | B6.129S2(Cg)-Ppargtm1Avp/Ieg |
| Alternative name | 129(B6)-PpargP465L |
| Strain type | Targeted Mutant Strains : Knock-in |
| Allele/Transgene symbol | Ppargtm1Avp, |
| Gene/Transgene symbol | Pparg |
| Provider | Tobias Stoeger |
| Provider affiliation | Institute of Lung Biology and Disease (iLBD), Comprehensive Pneumology Center, Helmholtz Zentrum München |
| Genetic information | According to the human mutation P467L (PubMed ID: 12663460), a targeting construct with a C-to-T point mutation in exon 6 of the mouse Pparg gene was generated by site-directed mutagenesis. A neomycin selection cassette flanked by two FRT sites was incorporated into intron 6 with two thymidine kinase genes positioned at the 5' and 3' ends of the flanking sequence. The targeting construct was transfected into a TBV2 (129/SvPas) ES cell line and homologously recombined clones were selected using G418/ganciclovir. Chimeras with successful germ-line transmission were bred to C57BL/6 mice to produce mice heterozygous for the point mutation. Removal of the neomycin selection cassette in intron 6 was performed by breeding mice heterozygous for the P465L Pparg mutation to FLP transgenic mice (for details see PubMed ID: 17003330). |
| Phenotypic information | Homozygous transmission of P465L Pparg mutation results in embryonic lethality. Heterozygous P465L Pparg matings produce an altered Mendelian ratio (wt/wt 28%, P465L/wt 72%, and P465L/P465L 0%), demonstrating that homozygous transmission of the P465L Pparg allele was embryonic lethal. Heterozygous mice grow normally and have normal total adipose tissue weight. However, they have reduced interscapular brown adipose tissue and intra-abdominal fat mass, and increased extra-abdominal subcutaneous fat, compared with wild-type mice. They have normal plasma glucose levels and insulin sensitivity, and increased glucose tolerance. However, during high-fat feeding, their plasma insulin levels are mildly elevated in association with a significant increase in pancreatic islet mass. They are hypertensive, and expression of the angiotensinogen gene is increased in their subcutaneous adipose tissues. The effects of P465L on blood pressure, fat distribution, and insulin sensitivity are the same in both male and female mice, regardless of diet and age (see PubMed ID: 15254591 for details). |
| Breeding history | Mice have been backcrossed for 9 generations to C57BL/6J. |
| References |
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| Homozygous fertile | no |
| Homozygous viable | no |
| Homozygous matings required | no |
| Immunocompromised | no |
| Archiving centre | Helmholtz Zentrum Muenchen - German Research Center for Environmental Health (GmbH), Oberschleißheim, Germany |
| Animals used for archiving | heterozygous C57BL/6J, wild-type C57BL/6J |
| Stage of embryos | 2-cell |
Orphanet associated rare diseases, based on orthologous gene matching
