Mice that are homozygous for this Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) knock-out mutation exhibit some postnatal lethality, impaired mitochondrial function and gluconeogenesis, are hypermetabolic, hyperactive, and sensitive to cold temperatures. This mutant mouse strain may be useful in studies of metabolic homeostasis, resistance to obesity, hyperactivity and behavior, mitochondrial impairment and neurodegeneration, and heart failure.
Bruce M Spiegelman, Dana-Farber Cancer Institute/Harvard Medical School
Genetic Background | Generation |
---|---|
N10+N1F11
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Ppargc1a | peroxisome proliferative activated receptor, gamma, coactivator 1 alpha |
Starting at:
$255.00 Domestic price for female 4-week |
333.51 Domestic price for breeder pair |
Mice that are homozygous for this targeted mutation are fertile, normal in size and do not display any gross physical or behavioral abnormalities. Approximately half of homozygotes exhibit postnatal lethality. The Donating Investigator reports maintaining homozygous pups at a higher temperature (77°F) increases their survival. No gene product (mRNA or protein) is detected by RNA hybridization, real-time PCR analysis of skeletal muscle or liver, or Western blot analysis of brown fat. Histological examination of the brown fat from homozygotes reveals abnormal accumulation of large lipid droplets. Examination of brain tissue shows spongiform lesions and gliosis. When fed a high fat diet homozygotes have increased insulin sensitivity, glucose tolerance and reduced body weight. After 24 hours of fasting, homozygotes develop mild hypoglycemia. Mutants have impaired mitochondrial function and gluconeogenesis and are hypermetabolic as well as hyperactive. Homozygotes are unable to survive exposure to 4°C for more than 6 hours. Exaggerated startle response, stimulus induced myoclonus, dystonic posturing, and limb clasping are also observed. Transverse aortic constriction (TAC) results in dilated cardiomyopathy and development of heart failure. The Donating Investigator reports that heterozygote X heterozygote crosses yields less than the expected Mendelian ratio (the observed ratio is 1 homozygote in 8); and homozygous mice are more likely to have litters disappear or die after birth. This mutant mouse strain may be useful in studies of metabolic homeostasis, resistance to obesity, hyperactivity and behavior, mitochondrial impairment, neurodegeneration, and heart failure.
A loxP site flanked targeting vector containing hygromycin resistance and thymidine kinase genes utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 5 of the targeted gene, and another loxP site was inserted upstream of exon 3. This 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 C57BL/6 mice. The resulting offspring were then crossed to transgenic mice (on the C57BL/6 genetic background) expressing Cre recombinase under the control of the zona pellucida 3 (Zp3) promoter to remove exons 3 through 5 and the selection cassette. Heterozygotes were crossed to generate homozygotes. The donating investigator reported that the mice were then backcrossed to C57BL/6 (see SNP note below) for 9 generations before arriving at The Jackson Laboratory.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
Allele Name | targeted mutation 1, Bruce M Spiegelman |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | PGC-1alpha- |
Gene Symbol and Name | Ppargc1a, peroxisome proliferative activated receptor, gamma, coactivator 1 alpha |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | 5 |
Molecular Note | This allele resulted from the crossing of Ppargc1atm2Brsp with mice expressing cre recombinase in the germline. Exons 3-5 were removed from the locus. Northern and Western blot analyses indicated a lack of transcript and protein in mutants. |
Mutations Made By | Bruce Spiegelman, Dana-Farber Cancer Institute/Harvard Medical School |
When maintaining a live colony, these mice can be bred as homozygotes, however approximately 50% of homozygotes exhibit postnatal lethality. The Donating Investigator reports maintaining homozygous pups at a higher temperature (77°F) increases their survival; heterozygote X heterozygote crosses yields less than the expected Mendelian ratio (the observed ratio is 1 homozygote in 8); and homozygous mice are more likely to have litters disappear or die after birth.
When using the PGC-1alpha KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #008597 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous or wild-type for Ppargc1a<tm1Brsp> |
Frozen Mouse Embryo | B6.129S4(FVB)-Ppargc1a<tm1Brsp>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S4(FVB)-Ppargc1a<tm1Brsp>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S4(FVB)-Ppargc1a<tm1Brsp>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129S4(FVB)-Ppargc1a<tm1Brsp>/J Frozen Embryo | $3373.50 |
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.
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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.