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| 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. | |||||||||||||||||||
- 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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Yaacov Barak, University of Pittsburgh Description
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.Development
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.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 002448 129S1/SvImJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Pparg
004584 B6.129-Ppargtm2Rev/J 006142 B6.129S4-Ppargtm1Rev/J 008227 B6.129S4-Ppargtm3Yba/J View Strains carrying other alleles of Pparg (3 strains)
Additional Web Information
Tet Expression Systems
Phenotype
Phenotype Information
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Lipodystrophy, Familial Partial, Type 3; FPLD3- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Lipodystrophy, Congenital Generalized, Type 2; CGL2
- 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.
Ppargtm2Yba/Pparg+
involves: 129S1/SvImJ * C57BL/6
- reproductive system phenotype
- reduced fertility
- mice exhibit poor fecundity after introgression onto a C57BL/6 background (MGI Ref ID J:125992)
- adipose tissue phenotype
- *normal* adipose tissue phenotype
- despite the development of dyslipidemia and severe insulin resistance, mice do not develop steatosis or type 2 diabetes (MGI Ref ID J:125992)
- abnormal brown adipose tissue morphology
- abnormal white adipose tissue morphology
- fibrotic white adipose tissue stroma is filled with fragmented lipid droplets and leukocytes (MGI Ref ID J:125992)
- remaining adipocytes have irregular shapes and range in size from overtly hypertrophic to minuscule cells (MGI Ref ID J:125992)
- however, defects were prevented by midgestational administration of doxycycline but adipocyte size does not revert following treatment with doxycycline (MGI Ref ID J:125992)
- abnormal white fat cell morphology
- remaining adipocytes have irregular shapes (MGI Ref ID J:125992)
- abnormal white fat cell size
- remaining adipocytes range in size from overtly hypertrophic to minuscule cells (MGI Ref ID J:125992)
- absent subcutaneous adipose tissue
- mice lack subcutaneous adipocytes (MGI Ref ID J:125992)
- decreased gonadal fat pad weight
- increased interscapular fat pad weight
- mice exhibit 'buffalo humps' comprised of swollen interscapular fat pads due to hypertrophy and unilocular lipid deposition in mutant brown adipocytes (MGI Ref ID J:125992)
- however, defects can be prevented by midgestational administration of doxycycline and reverted by a 6 week treatment with doxycycline (MGI Ref ID J:125992)
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype
- despite the development of dyslipidemia and severe insulin resistance, mice do not develop steatosis or type 2 diabetes (MGI Ref ID J:125992)
- hyperglycemia
- impaired glucose tolerance
- increased circulating cholesterol level
- increased circulating free fatty acid level
- increased circulating insulin level
- increased circulating triglyceride level
- insulin resistance (MGI Ref ID J:125992)
- endocrine/exocrine gland phenotype
- pancreas hyperplasia
- mice as old as 12 to 18 months exhibit hyperplasia with intact and insulin-laden pancreatic islets with hyperinsulinemia and normoglycemia (MGI Ref ID J:125992)
- pancreatic islet hyperplasia
- liver/biliary system phenotype
- abnormal hepatocyte morphology
- mice exhibit hepatocyte hypertrophy and vacuolization (MGI Ref ID J:125992)
- enlarged liver
- integument phenotype
- absent subcutaneous adipose tissue
- mice lack subcutaneous adipocytes (MGI Ref ID J:125992)
This mouse can be used to support research in many areas including:
Developmental Biology Research
Embryonic Lethality (Homozygous)
Metabolism Research
Lipid Metabolism
Research Tools
Metabolism Research
Tet Expression Systems
tTA/rtTA Expressing Strains
tTA/rtTA Responsive Strains
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Ppargtm2Yba | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, Yaacob Barak | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Ppargldi; | ||
| Mutation Made By | Yaacov Barak, University of Pittsburgh | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/SvJae | ||
| Site of Expression | Expression of tTA from the endogenous Pparg locus is detected in adipose tissue. | ||
| Expressed Gene | tetO, tet operator, | ||
| Expressed Gene | tTA, tetracycline-controlled transactivator, E. coli | ||
| The tetracycline-resistance gene (TetR), arose from chemically mutated Escherichia coli genome which was screened for tetracycline dependence (Gossen and Bujard, 1992). TetR was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16). The tetracycline-inhibitable transcription factor is a component of a bigenic system that allows doxycycline (a tetracycline analog) regulatable expression of genes that are under the direction of the tetracycline responsive promoter (TetOp)promoter. | |||
| 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. [MGI Ref ID J:125992] | ||
| 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
Ppargtm2Yba, Melt Curve Analysis
Ppargtm2Yba, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Kim S; Huang LW; Snow KJ; Ablamunits V; Hasham MG; Young TH; Paulk AC; Richardson JE; Affourtit JP; Shalom-Barak T; Bult CJ; Barak Y. 2007. A mouse model of conditional lipodystrophy. Proc Natl Acad Sci U S A 104(42):16627-32. [PubMed: 17921248] [MGI Ref ID J:125992]
Additional References
Ppargtm2Yba 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]
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, 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.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 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.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- 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* $2574.00 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.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- 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 | ||
| 002448 129S1/SvImJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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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| phone: | 207-288-6470 |
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