Description

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   08-JAN-10 Species laboratory mouse Generation N8+F5 (29-JUN-11) Generation Definitions   Donating Investigator Bruce Spiegelman,   Dana-Farber Cancer Institute

Description
These mice possess loxP sites on either side of exons 3-5 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 3-5 deleted in the cre-expressing tissue(s).

When bred to a strain expressing Cre recombinase specifically in the liver (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of hepatic heme biosynthesis and porphyrias.

When bred to a strain expressing Cre recombinase specifically in skeletal muscle, this mutant mouse strain may be useful in studies of neuromuscular junction physiology and muscular dystrophy.

Development
A loxP site flanked targeting vector containing neomycin resistance and thymidine kinase genes was 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 ?Sv129? derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. The mice were then crossed to transgenic mice expressing Cre recombinase under the control of the adenovirus EIIa promoter (B6.FVB-Tg(EIIa-cre)C5379Lmgd/J) to remove the neo selection cassette. Mice that retained the loxP site flanked exons 3-5 were then bred to C57BL/6N mice for 7 generations. The EIIa-cre transgene has been removed. Upon arrival at The Jackson Laboratory the mice were crossed with C57BL/6NJ once to establish the colony.

Control Information

	Control
	005304 C57BL/6NJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ppargc1a

008597	B6.129-Ppargc1atm1Brsp/J
009662	B6.129X1-Ppargc1atm1Dpk/J
008231	C57BL/6-Tg(Ckm-Ppargc1a)31Brsp/J
012387	FVB-Tg(tetO-Ppargc1a)1Dpk/J

View Strains carrying other alleles of Ppargc1a     (4 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Ppargc1a^tm2Brsp/Ppargc1a^tm2Brsp Tg(Alb-cre)21Mgn/0

        involves: C57BL/6 * DBA   (conditional)

• cellular phenotype
• abnormal cell physiology
  • fasting-mediated induction of aminolevulinic acid synthase is decreased in mutants compared to wild-type   (MGI Ref ID J:115197)
• homeostasis/metabolism phenotype
• abnormal blood homeostasis
  • injection of lead chloride into fasted mice does not alter serum gamma-aminolevulinic acid (ALA) or porphobilinogen (PBG) in contrast to increased levels observed in wild-type   (MGI Ref ID J:115197)

View Research Applications

Research Applications

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

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences

Research Tools
Cardiovascular Research
      Cre-lox System
Cell Biology Research
Cre-lox System
      loxP-flanked Sequences
Metabolism Research
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ppargc1atm2Brsp
Allele Name		targeted mutation 2, Bruce M Spiegelman
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		PGC-1alphafl;
Mutation Made By		Bruce Spiegelman,   Dana-Farber Cancer Institute
Strain of Origin		129
ES Cell Line Strain		129
Gene Symbol and Name		Ppargc1a, peroxisome proliferative activated receptor, gamma, coactivator 1 alpha
Chromosome		5
Gene Common Name(s)		A830037N07Rik; ENSMUSG00000079510; Gm11133; LEM6; PGC-1(alpha); PGC-1v; PGC1; PGC1A; PPAR Gamma Coactivator-1; PPAR gamma coactivator 1; PPARGC1; Pgc-1alpha; Pgc-1alphaa; Pgco1; RIKEN cDNA A830037N07 gene; predicted gene 11133; predicted gene, ENSMUSG00000079510;
Molecular Note		This allele is the parent of Ppargc1atm1Brsp in which exons 3-5 were flanked by loxP sites. A neo with a third loxP site was located downstream of the floxed exons. [MGI Ref ID J:93896]

Genotyping

Genotyping Information

Genotyping Protocols

Ppargc1a^tm2Brsp STD PCR, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lin J; Wu PH; Tarr PT; Lindenberg KS; St-Pierre J; Zhang CY; Mootha VK; Jager S; Vianna CR; Reznick RM; Cui L; Manieri M; Donovan MX; Wu Z; Cooper MP; Fan MC; Rohas LM; Zavacki AM; Cinti S; Shulman GI; Lowell BB; Krainc D; Spiegelman BM. 2004. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 119(1):121-35. [PubMed: 15454086]  [MGI Ref ID J:93896]

Additional References

Ppargc1a^tm2Brsp related

Estall JL; Kahn M; Cooper MP; Fisher FM; Wu MK; Laznik D; Qu L; Cohen DE; Shulman GI; Spiegelman BM. 2009. Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression. Diabetes 58(7):1499-508. [PubMed: 19366863]  [MGI Ref ID J:154344]

Estall JL; Ruas JL; Choi CS; Laznik D; Badman M; Maratos-Flier E; Shulman GI; Spiegelman BM. 2009. PGC-1alpha negatively regulates hepatic FGF21 expression by modulating the heme/Rev-Erb(alpha) axis. Proc Natl Acad Sci U S A 106(52):22510-5. [PubMed: 20018698]  [MGI Ref ID J:156463]

Finley LW; Lee J; Souza A; Desquiret-Dumas V; Bullock K; Rowe GC; Procaccio V; Clish CB; Arany Z; Haigis MC. 2012. Skeletal muscle transcriptional coactivator PGC-1alpha mediates mitochondrial, but not metabolic, changes during calorie restriction. Proc Natl Acad Sci U S A 109(8):2931-6. [PubMed: 22308395]  [MGI Ref ID J:182618]

Fisher FM; Estall JL; Adams AC; Antonellis PJ; Bina HA; Flier JS; Kharitonenkov A; Spiegelman BM; Maratos-Flier E. 2011. Integrated Regulation of Hepatic Metabolism by Fibroblast Growth Factor 21 (FGF21) in Vivo. Endocrinology 152(8):2996-3004. [PubMed: 21712364]  [MGI Ref ID J:174843]

Fisher FM; Kleiner S; Douris N; Fox EC; Mepani RJ; Verdeguer F; Wu J; Kharitonenkov A; Flier JS; Maratos-Flier E; Spiegelman BM. 2012. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 26(3):271-81. [PubMed: 22302939]  [MGI Ref ID J:181337]

Geng T; Li P; Okutsu M; Yin X; Kwek J; Zhang M; Yan Z. 2010. PGC-1alpha plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle. Am J Physiol Cell Physiol 298(3):C572-9. [PubMed: 20032509]  [MGI Ref ID J:157663]

Handschin C; Kobayashi YM; Chin S; Seale P; Campbell KP; Spiegelman BM. 2007. PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Genes Dev 21(7):770-83. [PubMed: 17403779]  [MGI Ref ID J:120376]

Handschin C; Lin J; Rhee J; Peyer AK; Chin S; Wu PH; Meyer UA; Spiegelman BM. 2005. Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha. Cell 122(4):505-15. [PubMed: 16122419]  [MGI Ref ID J:115197]

Jager S; Handschin C; St-Pierre J; Spiegelman BM. 2007. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1{alpha}. Proc Natl Acad Sci U S A 104(29):12017-22. [PubMed: 17609368]  [MGI Ref ID J:123153]

Kleiner S; Mepani RJ; Laznik D; Ye L; Jurczak MJ; Jornayvaz FR; Estall JL; Chatterjee Bhowmick D; Shulman GI; Spiegelman BM. 2012. Development of insulin resistance in mice lacking PGC-1alpha in adipose tissues. Proc Natl Acad Sci U S A 109(24):9635-40. [PubMed: 22645355]  [MGI Ref ID J:185521]

Lucas EK; Dougherty SE; McMeekin LJ; Trinh AT; Reid CS; Cowell RM. 2012. Developmental alterations in motor coordination and medium spiny neuron markers in mice lacking pgc-1alpha. PLoS One 7(8):e42878. [PubMed: 22916173]  [MGI Ref ID J:190053]

Patten IS; Rana S; Shahul S; Rowe GC; Jang C; Liu L; Hacker MR; Rhee JS; Mitchell J; Mahmood F; Hess P; Farrell C; Koulisis N; Khankin EV; Burke SD; Tudorache I; Bauersachs J; del Monte F; Hilfiker-Kleiner D; Karumanchi SA; Arany Z. 2012. Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature 485(7398):333-8. [PubMed: 22596155]  [MGI Ref ID J:184748]

Rasbach KA; Gupta RK; Ruas JL; Wu J; Naseri E; Estall JL; Spiegelman BM. 2010. PGC-1{alpha} regulates a HIF2{alpha}-dependent switch in skeletal muscle fiber types. Proc Natl Acad Sci U S A :. [PubMed: 21106753]  [MGI Ref ID J:167144]

Shoag J; Haq R; Zhang M; Liu L; Rowe GC; Jiang A; Koulisis N; Farrel C; Amos CI; Wei Q; Lee JE; Zhang J; Kupper TS; Qureshi AA; Cui R; Han J; Fisher DE; Arany Z. 2013. PGC-1 coactivators regulate MITF and the tanning response. Mol Cell 49(1):145-57. [PubMed: 23201126]  [MGI Ref ID J:194191]

Tran M; Tam D; Bardia A; Bhasin M; Rowe GC; Kher A; Zsengeller ZK; Akhavan-Sharif MR; Khankin EV; Saintgeniez M; David S; Burstein D; Karumanchi SA; Stillman IE; Arany Z; Parikh SM. 2011. PGC-1alpha promotes recovery after acute kidney injury during systemic inflammation in mice. J Clin Invest 121(10):4003-14. [PubMed: 21881206]  [MGI Ref ID J:178232]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   08-JAN-10
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	005304 C57BL/6NJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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