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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N15p Donating Investigator Yaacov Barak, The Jackson Laboratory Description
All mice homozygous for this targeted mutation die after gestational day 9.5 from severe placental defects and myocardial thinning. Heterozygotes are viable and fertile. White adipose tissue from heterozygous mice display approximately half the mRNA expression compared to wildtype. Tracer-determined glucose disposal rates and hepatic glucose production show that peripheral tissues and livers from heterozygotes are more sensitive to the effects of insulin than wildtype. This mutation eliminates both DNA-binding and ligand-binding functions of the endogenous gene, concomitantly generating a lacZ reporter that faithfully recapitulates the endogenous expression pattern. Heterozygous mice or homozygous embryo-derived cells may be useful in studies of embryo and placental development, diabetes, atherosclerosis, inflammation, and for beta-galactosidase reporter function of the endogenous gene.Development
A targeting vector was designed to insert a lacZ-neomycin resistance cassette into the second coding exon of the endogenous gene, just upstream of the DNA-binding domain. This construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted cells were injected into C57BL/6 blastocysts. Chimeric mice were backcrossed to C57BL/6 mice for more than 14 generations.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (176 strains)
008079 129S-Ppargtm2Yba/J 004584 B6.129-Ppargtm2Rev/J 008227 B6.129S4-Ppargtm3Yba/J
Additional Web Information
Congenic Nomenclature
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
NOT Lipodystrophy, Familial Partial, Type 3; FPLD3 - No similarity to the expected human disease phenotype was found.4
4 One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of those genes, but the phenotype did not resemble the disease.
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Ppargtm1Rev/Pparg+
involves: 129S4/SvJae * C57BL/6J
- homeostasis/metabolism phenotype
- abnormal glucose homeostasis (MGI Ref ID J:60354)
- increased insulin sensitivity (MGI Ref ID J:60354)
- male heterozygotes are apparently healthy and exhibit no significant differences in body weight, fat-pad, basal fasting glucose and insulin levels or FFA levels relative to wild-type mice
- unexpectedly, during oral glucose tolerance tests, heterozygotes are able to maintain wild-type glucose levels, despite a significant reduction in plasma insulin concentrations
- during glucose clamp experiments, heterozygotes show a 30% increase in the insulin-induced glucose disposal rate relative to wild-type mice
- similarly, heterozygotes exhibit a significant increase in insulin-induced suppression of hepatic glucose production relative to wild-type mice
- improved insulin sensitivity may be associated with increased serum leptin levels, as heterozygotes do show a significant increase in leptin mRNA expression
Ppargtm1Rev/Ppargtm1Rev
involves: 129S4/SvJae
- lethality-prenatal/perinatal
- embryonic lethality during organogenesis (MGI Ref ID J:58223)
- at E9.5 or earlier, homozygous mutant embryos are recovered at the expected Mendelian ratio and appear normal in both size and gross morphology
- however, all mutant embryos obtained after E9.5 are dead and display progressive necrosis
- embryogenesis phenotype
- abnormal placenta morphology (MGI Ref ID J:58223)
- abnormal chorionic plate morphology (MGI Ref ID J:58223)
- at E9.5, mutant embryos display abnormal thickening of the chorionic plate, with poorly differentiated chorionic villi and reduced hemotrichorial layer characteristics
- abnormal placenta labyrinth morphology (MGI Ref ID J:58223)
- at E9.5, mutant embryos display a maturation block in labyrinthine trophoblast, with an abnormally thick trophoblast tissue retaining features of the early labyrinthine parenchyma
- at E9.5, homozygotes show a dramatic decrease of lipid droplet accumulation in the three cell-layered labyrinthine barrier, with scarce lipid droplets found in presumptive hemotrichorial layers I and II, and miniscule lipid droplets found in layer III
- abnormal placental labyrinth vasculature morphology (MGI Ref ID J:58223)
- at E9.5, mutant placentas exhibit abnormal fetal and maternal vascular networks, with fetal vessels rarely permeating the presumptive labyrinth
- maternal blood sinuses appear frequently dilated, ruptured, and thus adjoined within mutant placentas, often forming a continuous blood pool throughout the entire zone
- maternal erythrocytes, normally restricted to the sinuses, are noted throughout the cytoplasms of cells in the mutant junctional zone, indicating obvious erythrophagocytic activity of the trophoblasts lining the maternal sinuses
- abnormal trophoblast layer morphology (MGI Ref ID J:58223)
- at E9.5, homozygotes display failure of fetal vessel permeation, phagocytosis of maternal blood cells, incomplete epithelialization of the labyrinthine barrier, and loose endothelial trophoblast contacts
- abnormal trophoblast giant cells (MGI Ref ID J:58223)
- at E9.5, the mutant trophoblast epithelium is less compact while the fetal endothelium is detached from hemotrichorial layer III
- cardiovascular system phenotype
- abnormal fetal cardiomyocyte morphology (MGI Ref ID J:58223)
- notably at E9.5, numerous mitochondria in the ventricular subepicardial myocytes appear significantly inflated and irregularly shaped, suggesting mitochondrial cardiomyopathy
- abnormal myocardial fiber morphology (MGI Ref ID J:58223)
- at E9.5, homozygotes exhibit premature differentiation of ventricular subepicardial myocytes, as shown by frequent tandem sarcomers, separated by multiple Z lines, crossing cell boundaries through intercalated discs
- abnormal myocardial trabeculae morphology (MGI Ref ID J:58223)
- at E9.5, homozygotes display degeneration of the trabecular zone
- abnormal ventricular septum morphology (MGI Ref ID J:58223)
- at E9.5, homozygotes display severe thinning of the ventricular septum
- thin myocardial wall (MGI Ref ID J:58223)
- thin ventricular wall (MGI Ref ID J:58223)
- at E9.5, homozygotes display severe thinning of the ventricular wall
- ventricular hypoplasia (MGI Ref ID J:58223)
- at E9.5, homozygotes exhibit severe thinning of the compact zone of the ventricular myocardium
- muscle phenotype
- abnormal myocardial fiber morphology (MGI Ref ID J:58223)
- at E9.5, homozygotes exhibit premature differentiation of ventricular subepicardial myocytes, as shown by frequent tandem sarcomers, separated by multiple Z lines, crossing cell boundaries through intercalated discs
- abnormal myocardial trabeculae morphology (MGI Ref ID J:58223)
- at E9.5, homozygotes display degeneration of the trabecular zone
- thin myocardial wall (MGI Ref ID J:58223)
This mouse can be used to support research in many areas including:
Cardiovascular Research
Atherosclerosis
Heart Abnormalities
Developmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects (heart)
Diabetes and Obesity Research
Impaired Insulin Processing
Research Tools
lacZ Expression
Apoptosis Research
Cardiovascular Research
Developmental Biology Research
Diabetes and Obesity Research (lacZ)
Immunology and Inflammation Research
Internal/Organ Research
Metabolism Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Ppargtm1Rev | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Ronald M Evans | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | PPARg-; | ||
| Mutation Made By | Ronald Evans, The Salk Inst for Biological Studies | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/SvJae | ||
| Site of Expression | lacZ expression closely mimics the patterns of the endogenous gene. | ||
| Gene Symbol and Name | Pparg, peroxisome proliferator activated receptor gamma | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | NR1C3; PPAR-gamma; PPARG1; PPARG2; PPARgamma; PPARgamma2; Ppar-gamma2; | ||
| General Note | Complementation of Ppargtm1Rev mutant embryos with wild-type placenta by tetraploid aggregation corrects the cardiac defect and extends viability to E12.5 (two mutants out of a total five), E15.5 (one out of ten) and at birth (one of six). Rescued embryos survive to term but exhibit a second lethal phase during the first week of life. Additional phenotypes include: a 30% reduction in body weight(P0-P4) and subsequent ill health (as shown by dehydration, weight loss and lethargy starting at P5) associated with lipodystrophy, a severly pale, distended and fatty liver, severe intestinal bleeding, and numerous focal hematomas throughout the brain (J:58223). | ||
| Molecular Note | In-frame insertion of a lac Z-neomycin resistance cassette into the second coding exon of the gene, just upstream of the DNA binding domain, eliminated both DNA-binding and ligand-binding functions of the receptor. Whole-mount beta-galactosidase assays revealed conspicuous beta-gal activivity in the interscapular brown fat pad of only E14.5 embryos carrying a targeted allele, but not in wild-type embryos [MGI Ref ID J:58223] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Ppargtm1Rev, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Additional References
Ppargtm1Rev relatedBarak Y; Nelson MC; Ong ES; Jones YZ; Ruiz-Lozano P; Chien KR; Koder A; Evans RM. 1999. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 4(4):585-95. [PubMed: 10549290] [MGI Ref ID J:58223]
Bright JJ; Natarajan C; Muthian G; Barak Y; Evans RM. 2003. Peroxisome proliferator-activated receptor-gamma-deficient heterozygous mice develop an exacerbated neural antigen-induced Th1 response and experimental allergic encephalomyelitis. J Immunol 171(11):5743-50. [PubMed: 14634082] [MGI Ref ID J:119331]
Kang K; Reilly SM; Karabacak V; Gangl MR; Fitzgerald K; Hatano B; Lee CH. 2008. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab 7(6):485-95. [PubMed: 18522830] [MGI Ref ID J:137033]
Miles PD; Barak Y; Evans RM; Olefsky JM. 2003. Effect of heterozygous PPARgamma deficiency and TZD treatment on insulin resistance associated with age and high-fat feeding. Am J Physiol Endocrinol Metab 284(3):E618-26. [PubMed: 12556354] [MGI Ref ID J:82488]
Miles PD; Barak Y; He W; Evans RM; Olefsky JM. 2000. Improved insulin-sensitivity in mice heterozygous for PPAR-gamma deficiency. J Clin Invest 105(3):287-92. [PubMed: 10675354] [MGI Ref ID J:60354]
Saez E; Olson P; Evans RM. 2003. Genetic deficiency in Pparg does not alter development of experimental prostate cancer. Nat Med 9(10):1265-1266. [PubMed: 12960963] [MGI Ref ID J:86096]
Shalom-Barak T; Nicholas JM; Wang Y; Zhang X; Ong ES; Young TH; Gendler SJ; Evans RM; Barak Y. 2004. Peroxisome proliferator-activated receptor gamma controls Muc1 transcription in trophoblasts. Mol Cell Biol 24(24):10661-9. [PubMed: 15572671] [MGI Ref ID J:95115]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mutant mice are bred with C57BL/6J or wildtype siblings. Homozygous mice die in utero.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
Additional Supply Details
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 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
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