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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N15p
Generation DefinitionsDonating Investigator Yaacov Barak, University of Pittsburgh 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 (255 strains)
008079 129S-Ppargtm2Yba/J 004584 B6.129-Ppargtm2Rev/J 008227 B6.129S4-Ppargtm3Yba/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
- No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.
Lipodystrophy, Familial Partial, Type 3; FPLD3
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Carotid Intimal Medial Thickness 1 (PPARG)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM (PPARG)
Obesity (PPARG)
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
- 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 (MGI Ref ID J:60354)
- unexpectedly, during oral glucose tolerance tests, heterozygotes are able to maintain wild-type glucose levels, despite a significant reduction in plasma insulin concentrations (MGI Ref ID J:60354)
- during glucose clamp experiments, heterozygotes show a 30% increase in the insulin-induced glucose disposal rate relative to wild-type mice (MGI Ref ID J:60354)
- similarly, heterozygotes exhibit a significant increase in insulin-induced suppression of hepatic glucose production relative to wild-type mice (MGI Ref ID J:60354)
- improved insulin sensitivity may be associated with increased serum leptin levels, as heterozygotes do show a significant increase in leptin mRNA expression (MGI Ref ID J:60354)
Ppargtm1Rev/Ppargtm1Rev
involves: 129S4/SvJae
- mortality/aging
- complete embryonic lethality during organogenesis
- embryogenesis phenotype
- abnormal placenta morphology (MGI Ref ID J:58223)
- abnormal chorionic plate morphology
- at E9.5, mutant embryos display abnormal thickening of the chorionic plate, with poorly differentiated chorionic villi and reduced hemotrichorial layer characteristics (MGI Ref ID J:58223)
- abnormal placenta labyrinth morphology
- 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 (MGI Ref ID J:58223)
- 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 (MGI Ref ID J:58223)
- abnormal placental labyrinth vasculature morphology
- at E9.5, mutant placentas exhibit abnormal fetal and maternal vascular networks, with fetal vessels rarely permeating the presumptive labyrinth (MGI Ref ID J:58223)
- maternal blood sinuses appear frequently dilated, ruptured, and thus adjoined within mutant placentas, often forming a continuous blood pool throughout the entire zone (MGI Ref ID J:58223)
- 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 (MGI Ref ID J:58223)
- abnormal trophoblast layer morphology
- 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 (MGI Ref ID J:58223)
- abnormal trophoblast giant cells
- at E9.5, the mutant trophoblast epithelium is less compact while the fetal endothelium is detached from hemotrichorial layer III (MGI Ref ID J:58223)
- cardiovascular system phenotype
- abnormal fetal cardiomyocyte morphology
- notably at E9.5, numerous mitochondria in the ventricular subepicardial myocytes appear significantly inflated and irregularly shaped, suggesting mitochondrial cardiomyopathy (MGI Ref ID J:58223)
- abnormal myocardial fiber morphology
- 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 (MGI Ref ID J:58223)
- abnormal myocardial trabeculae morphology
- at E9.5, homozygotes display degeneration of the trabecular zone (MGI Ref ID J:58223)
- abnormal placental labyrinth vasculature morphology
- at E9.5, mutant placentas exhibit abnormal fetal and maternal vascular networks, with fetal vessels rarely permeating the presumptive labyrinth (MGI Ref ID J:58223)
- maternal blood sinuses appear frequently dilated, ruptured, and thus adjoined within mutant placentas, often forming a continuous blood pool throughout the entire zone (MGI Ref ID J:58223)
- 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 (MGI Ref ID J:58223)
- thin interventricular septum
- at E9.5, homozygotes display severe thinning of the ventricular septum (MGI Ref ID J:58223)
- thin myocardium (MGI Ref ID J:58223)
- thin ventricle myocardium compact layer
- at E9.5, homozygotes exhibit severe thinning of the compact zone of the ventricular myocardium (MGI Ref ID J:58223)
- thin ventricular wall
- at E9.5, homozygotes display severe thinning of the ventricular wall (MGI Ref ID J:58223)
- muscle phenotype
- abnormal myocardial fiber morphology
- 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 (MGI Ref ID J:58223)
- abnormal myocardial trabeculae morphology
- at E9.5, homozygotes display degeneration of the trabecular zone (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 provided by MGI
| Allele Symbol | Ppargtm1Rev | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Ronald M Evans | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | PPARg-; 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. | ||
| Promoter | lacZ, beta-galactosidase, E. coli | ||
| 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] | ||
| Gene Symbol and Name | Pparg, peroxisome proliferator activated receptor gamma | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | CIMT1; GLM1; NR1C3; PPAR-gamma; PPARG1; PPARG2; PPARgamma; PPARgamma2; Ppar-gamma2; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Ppargtm1Rev, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Additional References
Ppargtm1Rev relatedArck P; Toth B; Pestka A; Jeschke U. 2010. Nuclear Receptors of the Peroxisome Proliferator-Activated Receptor (PPAR) Family in Gestational Diabetes: From Animal Models to Clinical Trials. Biol Reprod 83(2):168-76. [PubMed: 20427759] [MGI Ref ID J:161967]
Barak 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]
Szanto A; Balint BL; Nagy ZS; Barta E; Dezso B; Pap A; Szeles L; Poliska S; Oros M; Evans RM; Barak Y; Schwabe J; Nagy L. 2010. STAT6 transcription factor is a facilitator of the nuclear receptor PPARgamma-regulated gene expression in macrophages and dendritic cells. Immunity 33(5):699-712. [PubMed: 21093321] [MGI Ref ID J:167002]
Tsai YS; Tsai PJ; Jiang MJ; Chou TY; Pendse A; Kim HS; Maeda N. 2009. Decreased PPAR gamma expression compromises perigonadal-specific fat deposition and insulin sensitivity. Mol Endocrinol 23(11):1787-98. [PubMed: 19749155] [MGI Ref ID J:153891]
Tsai YS; Xu L; Smithies O; Maeda N. 2009. Genetic variations in peroxisome proliferator-activated receptor gamma expression affect blood pressure. Proc Natl Acad Sci U S A 106(45):19084-9. [PubMed: 19884495] [MGI Ref ID J:154767]
Wang P; Liu J; Li Y; Wu S; Luo J; Yang H; Subbiah R; Chatham J; Zhelyabovska O; Yang Q. 2010. Peroxisome proliferator-activated receptor {delta} is an essential transcriptional regulator for mitochondrial protection and biogenesis in adult heart. Circ Res 106(5):911-9. [PubMed: 20075336] [MGI Ref ID J:170872]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.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.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Embryos
Price (US dollars $) Frozen Embryo $1600.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Embryos
Price (US dollars $) Frozen Embryo $2080.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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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.Ordering Information
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For Licensing and Use Restrictions view the link(s) below:
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Contact information
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| phone: | 207-288-6470 |
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JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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