These mice express tTA (tetracycline regulated transactivator) and a tetO-driven Flag-tagged Pparg from the endogenous Pparg locus. Although heterozygous mice exhibit lipodystrophy, hyperinsulinemia, pancreatic islet hyperplasia, and severe glucose intolerance, they do not develop steatosis or type II diabetes. Treatment with doxycycline prevents these phenotypes when administered starting at midgestation whereas a 6 week treatment administered to pubertal heterozygotes reverses most of these phenotypes. This strain may be useful in studies of lipodystrophy.
Yaacov Barak, University of Pittsburgh
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Transactivator) | Pparg | peroxisome proliferator activated receptor gamma |
These mice express tTA (tetracycline regulated transactivator) and a tetO-driven Flag-tagged Pparg from the endogenous Pparg locus. A fusion transcript (including the 5' portion of Pparg, IRES and tTA (AF1-IRES-tTA)), a Flag-Pparg transcript and a wildtype transcript are detected by Northem blot analysis of white adipose tissue from heterozygotes. The fusion transcript of AF1-IRES-tTA is also detected in brown adipose tissue. Expression of tTA is detected in adipose tissue by Western blot analysis. No Flag-PPARG1 protein was detected in adipose tissue. Weak expression of tTA and the Flag-Pparg transcript is observed in placenta and liver. Endogenous PPARG2 protein is reduced in adipose tissues of heterozygotes. Heterozygotes exhibit "buffalo humps" (swollen interscapular fat pads swollen by hypertrophy and unilocular lipid deposition in mutant brown adipocytes), absence of subcutaneous adipocytes, reduced gonadal white adipose tissue, irregularly residual adipocyte shape and size, and fibrotic white adipose tissue stroma with leukocytic infiltration of the adipose tissue. Although, mutant mice have hyperinsulinemia, pancreatic islet hyperplasia, severe glucose intolerance, and hepatomegaly, they do not develop steatosis or type II diabetes. Prepubertal male heterozygotes exhibit hyperglycemia which normalizes with age. Treatment with doxycycline prevents this phenotype when administered starting at midgestation. A 6 week doxycycline treatment administered to pubertal heterozygotes reverses most of the phenotype, except the reduction in white adipose tissue. Mice that are homozygous for the targeted mutation are not viable. This mutant mouse strain may be useful in studies of lipodystrophy.
The Ldi cassette, containing IRES sequence, tTA (tetracycline regulated transactivator), PGK-neo, polyA, and a flag-tagged Pparg (peroxisome proliferator activated receptor gamma) cDNA sequence, was used to replace exon 2. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129S1/SvImJ mice. The Donating Investigator maintained the strain as a heterozygote because of the homozygous lethal phenotype.
Expressed Gene | tTA, tetracycline-controlled transactivator, E. coli |
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Site of Expression | Expression of tTA from the endogenous Pparg locus is detected in adipose tissue. |
Allele Name | targeted mutation 2, Yaacob Barak |
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Allele Type | Targeted (Transactivator) |
Allele Synonym(s) | Ppargldi; Ppargtm2Yba |
Gene Symbol and Name | Pparg, peroxisome proliferator activated receptor gamma |
Gene Synonym(s) | |
Promoter | tetO, tet operator, |
Expressed Gene | tTA, tetracycline-controlled transactivator, E. coli |
Site of Expression | Expression of tTA from the endogenous Pparg locus is detected in adipose tissue. |
Strain of Origin | 129S4/SvJae |
Chromosome | 6 |
Molecular Note | Exon 2 was replaced with an Idi cassette that contains an IRES-tTA, neo, poly-adenylation signal, TetO and flag-tagged cDNA. While expression is modest in adipose tissue, it is poor in the liver and placenta. |
Mutations Made By | Yaacov Barak, University of Pittsburgh |
When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes are not viable. The Donating Investigator maintained the strain by crossing heterozygous males, between 3 and 5 months of age, to wildtype 129S1/SvImJ females. This strain has a problematic fecundity with only about half of the heterozygous male animals between 3 and 5 months of age reproducing.
When using the 129S-Ppargtm2(tTA)Yba/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008079 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or Wild-type for Pparg<tm2Yba> |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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