Overview

Also Known As: PPARgamma KO

PPAR gamma deficiency in these knock-out mice interferes with terminal differentiation of the trophoblast and placental vascularization, leading to myocardial thinning and death by E10.0. A lacZ reporter in these mice recapitulates the endogenous Pparg expression pattern.

Donating Investigator

Yaacov Barak, University of Pittsburgh

Genetic overview

Genetic Background	Generation

Pparg^tm1Rev

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Pparg	peroxisome proliferator activated receptor gamma

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Research Applications

Research Tools
Diabetes and Obesity Research
Developmental Biology Research
Cardiovascular Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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 Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Pparg^tm1Rev

Allele Symbol: Pparg^tm1Rev

Allele Name	targeted mutation 1, Ronald M Evans
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Ronald M Evans; Pparg^tm1Rev
Gene Symbol and Name	Pparg, peroxisome proliferator activated receptor gamma
Gene Synonym(s)	NR1C3; CIMT1; PPARG2; PPAR-gamma; Ppar-gamma2; PPARG1; PPARgamma; PPARgamma2; GLM1; Nr1c3
Promoter	lacZ, beta-galactosidase, E. coli
Site of Expression	lacZ expression closely mimics the patterns of the endogenous gene.
Strain of Origin	129S4/SvJae
Chromosome	6
General Note	Complementation of Pparg^tm1Rev 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
Mutations Made By	Ronald Evans, The Salk Inst for Biological Studies

Disease/Phenotype

Disease Terms

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.

familial partial lipodystrophy

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Research Tools
- lacZ Expression
- Apoptosis Research
- Diabetes and Obesity Research
  - lacZ
- Developmental Biology Research
- Immunology, Inflammation and Autoimmunity Research
- Metabolism Research
- Internal/Organ Research
- Cardiovascular Research
Diabetes and Obesity Research
- Impaired Insulin Processing
Developmental Biology Research
- Embryonic Lethality (Homozygous)
- Internal/Organ Defects
  - heart
Cardiovascular Research
- Heart Abnormalities
- Atherosclerosis

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Pparg^tm1Rev/Pparg^tm1Rev
involves: 129S4/SvJae

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

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

abnormal myocardial trabeculae morphology
- at E9.5, homozygotes display degeneration of the trabecular zone

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
- 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

thin interventricular septum
- at E9.5, homozygotes display severe thinning of the ventricular septum

thin myocardium

thin ventricle myocardium compact layer
- at E9.5, homozygotes exhibit severe thinning of the compact zone of the ventricular myocardium

thin ventricular wall
- at E9.5, homozygotes display severe thinning of the ventricular wall

embryo phenotype

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

abnormal placenta hemotrichorial membrane morphology
- 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 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

abnormal placenta morphology

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
- 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 giant cell morphology
- at E9.5, the mutant trophoblast epithelium is less compact while the fetal endothelium is detached from hemotrichorial layer III

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance
- 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

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

abnormal myocardial trabeculae morphology
- at E9.5, homozygotes display degeneration of the trabecular zone

thin myocardium

thin ventricle myocardium compact layer
- at E9.5, homozygotes exhibit severe thinning of the compact zone of the ventricular myocardium

Genotype: Pparg^tm1Rev/Pparg⁺
involves: 129S4/SvJae * C57BL/6J

homeostasis/metabolism phenotype

abnormal glucose homeostasis

increased insulin sensitivity
- during glucose clamp experiments, heterozygotes show a 30% increase in the insulin-induced glucose disposal rate 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
- 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
- similarly, heterozygotes exhibit a significant increase in insulin-induced suppression of hepatic glucose production 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

References

Additional - Pparg^tm1Rev related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Pparg^tm1Rev
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mutant mice are bred with C57BL/6J or wildtype siblings. Homozygous mice die in utero.
- Additional Breeding and Husbandry Support
Citation
When using the PPARgamma KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006142 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or Wild-type for Pparg<tm1Rev>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

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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.

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Also Known As: PPARgamma KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Ppargtm1Rev

Allele Symbol: Ppargtm1Rev

Disease Terms

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.

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Ppargtm1Rev/Ppargtm1Revinvolves: 129S4/SvJae

cardiovascular system phenotype

embryo phenotype

mortality/aging

muscle phenotype

Genotype: Ppargtm1Rev/Pparg+involves: 129S4/SvJae * C57BL/6J

homeostasis/metabolism phenotype

References

Additional - Ppargtm1Rev related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Pparg^tm1Rev

Allele Symbol: Pparg^tm1Rev

Genotype: Pparg^tm1Rev/Pparg^tm1Rev
involves: 129S4/SvJae

Genotype: Pparg^tm1Rev/Pparg⁺
involves: 129S4/SvJae * C57BL/6J

Additional - Pparg^tm1Rev related