IMPC phenotypes (gene matching)
B6.129S2(Cg)-Ppargtm1Avp/Ieg
| Status | Available to order |
| EMMA ID | EM:05573 |
| Citation information | RRID:IMSR_EM:05573 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information. |
| 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 |
Information from provider
| 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 |
|
| Homozygous fertile | no |
| Homozygous viable | no |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Helmholtz Zentrum Muenchen - German Research Center for Environmental Health (GmbH), Oberschleißheim, Germany |
| Animals used for archiving | heterozygous C57BL/6J males, wild-type C57BL/6J females |
| Stage of embryos | 2-cell |
Disease and phenotype information
Orphanet associated rare diseases, based on orthologous gene matching
- Berardinelli-Seip congenital lipodystrophy / Orphanet_528
- PPARG-related familial partial lipodystrophy / Orphanet_79083
MGI phenotypes (allele matching)
- abnormal adipose tissue distribution / MGI
- abnormal triglyceride level / MGI
- increased circulating triglyceride level / MGI
- abnormal lipid homeostasis / MGI
- hepatic steatosis / MGI
- increased liver weight / MGI
- decreased adiponectin level / MGI
- homeostasis/metabolism phenotype / MGI
- growth/size/body region phenotype / MGI
- abnormal fat cell morphology / MGI
- preweaning lethality, complete penetrance / MGI
MGI phenotypes (gene matching)
- abnormal adipose tissue distribution / MGI
- abnormal bone marrow development / MGI
- abnormal triglyceride level / MGI
- hypertension / MGI
- abnormal heart development / MGI
- abnormal myocardial fiber morphology / MGI
- thin ventricular wall / MGI
- enlarged liver / MGI
- abnormal hepatocyte morphology / MGI
- decreased body weight / MGI
- hyperactivity / MGI
- hyperlipidemia / MGI
- increased circulating triglyceride level / MGI
- increased circulating free fatty acid level / MGI
- hyperglycemia / MGI
- abnormal circulating alanine transaminase level / MGI
- extended life span / MGI
- decreased embryo size / MGI
- abnormal placenta morphology / MGI
- abnormal placenta development / MGI
- placental labyrinth hypoplasia / MGI
- abnormal placenta labyrinth morphology / MGI
- postnatal growth retardation / MGI
- decreased brown adipose tissue amount / MGI
- decreased white adipose tissue amount / MGI
- abnormal humoral immune response / MGI
- reduced fertility / MGI
- abnormal glucose homeostasis / MGI
- increased circulating insulin level / MGI
- prenatal lethality / MGI
- premature death / MGI
- abnormal lipid homeostasis / MGI
- no abnormal phenotype detected / MGI
- abnormal myocardial trabeculae morphology / MGI
- decreased susceptibility to hepatic steatosis / MGI
- abnormal bone marrow morphology / MGI
- abnormal B cell physiology / MGI
- increased IgG level / MGI
- increased IgM level / MGI
- hepatic steatosis / MGI
- decreased circulating triglyceride level / MGI
- thin myocardium / MGI
- decreased circulating free fatty acid level / MGI
- decreased circulating insulin level / MGI
- abnormal retinal vasculature morphology / MGI
- increased systemic arterial blood pressure / MGI
- decreased systemic arterial blood pressure / MGI
- increased insulin sensitivity / MGI
- abnormal white adipose tissue morphology / MGI
- abnormal brown adipose tissue morphology / MGI
- increased liver weight / MGI
- no phenotypic analysis / MGI
- increased susceptibility to induced arthritis / MGI
- abnormal bone structure / MGI
- embryonic growth retardation / MGI
- increased incidence of tumors by chemical induction / MGI
- abnormal chorionic plate morphology / MGI
- increased adiponectin level / MGI
- decreased adiponectin level / MGI
- increased osteoblast cell number / MGI
- abnormal trophoblast layer morphology / MGI
- abnormal trophoblast giant cell morphology / MGI
- abnormal cell differentiation / MGI
- increased B cell proliferation / MGI
- abnormal response to injury / MGI
- increased circulating cholesterol level / MGI
- decreased circulating cholesterol level / MGI
- abnormal pancreatic islet morphology / MGI
- improved glucose tolerance / MGI
- impaired glucose tolerance / MGI
- insulin resistance / MGI
- abnormal gonadal fat pad morphology / MGI
- abnormal inguinal fat pad morphology / MGI
- increased circulating aspartate transaminase level / MGI
- liver/biliary system phenotype / MGI
- adipose tissue phenotype / MGI
- homeostasis/metabolism phenotype / MGI
- growth/size/body region phenotype / MGI
- immune system phenotype / MGI
- reproductive system phenotype / MGI
- skeleton phenotype / MGI
- pancreatic islet hyperplasia / MGI
- increased body temperature / MGI
- decreased body temperature / MGI
- increased circulating glucose level / MGI
- decreased susceptibility to diet-induced obesity / MGI
- decreased circulating leptin level / MGI
- increased circulating leptin level / MGI
- abnormal white adipose tissue physiology / MGI
- decreased body mass index / MGI
- increased fat cell size / MGI
- abnormal epididymal fat pad morphology / MGI
- abnormal bone ossification / MGI
- abnormal osteoblast differentiation / MGI
- leukostasis / MGI
- increased interferon-gamma secretion / MGI
- increased interleukin-2 secretion / MGI
- abnormal fetal cardiomyocyte morphology / MGI
- abnormal placental labyrinth vasculature morphology / MGI
- absent subcutaneous adipose tissue / MGI
- decreased subcutaneous adipose tissue amount / MGI
- decreased total fat pad weight / MGI
- pancreas hyperplasia / MGI
- abnormal fat cell morphology / MGI
- abnormal brown fat cell morphology / MGI
- abnormal white fat cell morphology / MGI
- increased brown fat cell size / MGI
- decreased brown fat cell lipid droplet size / MGI
- decreased white fat cell number / MGI
- abnormal white fat cell size / MGI
- decreased white fat cell size / MGI
- decreased brown fat lipid droplet number / MGI
- abnormal endocrine pancreas morphology / MGI
- decreased gonadal fat pad weight / MGI
- decreased inguinal fat pad weight / MGI
- increased interscapular fat pad weight / MGI
- decreased retroperitoneal fat pad weight / MGI
- increased liver triglyceride level / MGI
- increased sensitivity to xenobiotic induced morbidity/mortality / MGI
- decreased total body fat amount / MGI
- thin ventricle myocardium compact layer / MGI
- thin interventricular septum / MGI
- increased trabecular bone mass / MGI
- abnormal circadian temperature homeostasis / MGI
- postnatal lethality, incomplete penetrance / MGI
- prenatal lethality, complete penetrance / MGI
- embryonic lethality, complete penetrance / MGI
- embryonic lethality during organogenesis, complete penetrance / MGI
- preweaning lethality, complete penetrance / MGI
- lipodystrophy / MGI
- decreased food intake / MGI
- increased fluid intake / MGI
- abnormal placenta hemotrichorial membrane morphology / MGI
- decreased white adipose tissue mass / MGI
- decreased brown adipose tissue mass / MGI
- increased adipocyte glucose uptake / MGI
- decreased muscle cell glucose uptake / MGI
Literature references
- Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in mice.;Gray Sarah L, Nora Edoardo Dalla, Grosse Johannes, Manieri Monia, Stoeger Tobias, Medina-Gomez Gema, Burling Keith, Wattler Sigrid, Russ Andreas, Yeo Giles S H, Chatterjee V Krishna, O'Rahilly Stephen, Voshol Peter J, Cinti Saverio, Vidal-Puig Antonio, ;2006;Diabetes..;55;2669-77; 17003330