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 Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N7pN1 Generation Definitions   Donating Investigator Daniel Kelly,   Burnham Institute for Medical Research

Description
This transgenic strain expresses mouse Ppara (peroxisome proliferator activated receptor alpha) cDNA carrying a C-terminal FLAG tag under the control of the mouse Ckm (creatine kinase, muscle) promoter. Expression levels in this "high expression" (HE) line are increased approximately 100-fold over endogenous levels. Highest expression is found in fast-twitch muscle and less expression occurs in heart and soleus. Hemizygotes develop glucose intolerance (as early as 6 weeks of age) and insulin resistance despite being protected from diet-induced obesity. This strain may be useful in studies of diabetes, obesity, and muscle lipotoxicity.

Development
The mouse Ckm (creatine kinase, muscle) promoter drives expression of mouse Ppara (peroxisome proliferator activated receptor alpha) cDNA carrying a C-terminal FLAG tag. The transgenic construct was introduced to B6CBAF1 hybrid embryos. This strain was backcrossed to C57BL/6 at least 7 times by the donating laboratory. This is a high expressor line.

Related Strains

Strains carrying other alleles of Ckm

009651	B6.Cg-Sgcatm1Kcam Tg(Ckm-SGCE)1Kcam/J
014146	B6.Cg-Tg(Ckm-DYSF)3Kcam/J
006475	B6.FVB(129S4)-Tg(Ckmm-cre)5Khn/J
006781	C57BL/6-Tg(Ckm-DGAT2)10Far/J
008231	C57BL/6-Tg(Ckm-Ppargc1a)31Brsp/J
021199	FVB-Tg(Ckm-Chrnd*S268F)1Cgz/J
019931	FVB-Tg(Ckm-Chrne*L269F)5Cgz/J
016618	FVB-Tg(Ckm-IGF1R*K1003R)1Dlr/J
008737	FVB-Tg(Ckm-Ppargc1b)T37Brsp/J
006405	FVB-Tg(Ckmm-cre)5Khn/J

View Strains carrying other alleles of Ckm     (10 strains)

Strains carrying other alleles of Ppara

003580	129S4/SvJae-Pparatm1Gonz/J
012389	B6.Cg-Tg(Myh6-Ppara)404-3Dpk/J
012382	B6.Cg-Tg(Myh6-Ppara)404-4Dpk/J
008154	B6;129S4-Pparatm1Gonz/J

View Strains carrying other alleles of Ppara     (4 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Peroxisome Proliferator-Activated Receptor-Alpha; PPARA   (PPARA)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Tg(Ckm-Ppara)HEDpk/0

        involves: C57BL/6 * CBA

• homeostasis/metabolism phenotype
• abnormal glucose homeostasis
  • in a hyperinsulinemic-euglycemic clamp study, peripheral glucose disposal is diminished compared to in wild-type mice   (MGI Ref ID J:129848)
• • impaired glucose tolerance
    • in a glucose tolerance test, glucose excursion is greater than in wild-type mice   (MGI Ref ID J:129848)
    • when fed a high fat diet, mice exhibit greater glucose intolerance compared with similarly treated wild-type mice   (MGI Ref ID J:129848)
    • however, inhibition of fatty acid oxidation improves glucose tolerance   (MGI Ref ID J:129848)
  • increased circulating glucose level
    • when mice are fed standard chow or fasted   (MGI Ref ID J:129848)
  • increased circulating insulin level
    • when mice are fed standard chow or fasted   (MGI Ref ID J:129848)
  • insulin resistance
    • when fed a high fat or standard diet   (MGI Ref ID J:129848)
• decreased susceptibility to diet-induced obesity
  • when fed a high fat diet   (MGI Ref ID J:129848)
• increased triglyceride level
  • within skeletal muscle when mice are fed a high fat diet   (MGI Ref ID J:129848)
• adipose tissue phenotype
• decreased abdominal adipose tissue amount
  • when fed a high fat diet   (MGI Ref ID J:129848)
• decreased subcutaneous adipose tissue amount
  • when fed a high fat diet   (MGI Ref ID J:129848)
• growth/size phenotype
• decreased susceptibility to diet-induced obesity
  • when fed a high fat diet   (MGI Ref ID J:129848)
• muscle phenotype
• abnormal muscle cell glucose uptake
  • basal and insulin-stimulated glucose uptake is reduced compared to in wild-type mice   (MGI Ref ID J:129848)
• integument phenotype
• decreased subcutaneous adipose tissue amount
  • when fed a high fat diet   (MGI Ref ID J:129848)

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Insulin Resistance
Obesity Without Diabetes
      diet-induced, resistant

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(Ckm-Ppara)HEDpk
Allele Name		transgene insertion HE, Daniel P Kelly
Allele Type		Transgenic (random, expressed)
Common Name(s)		MCK-PPARalpha (High expressor);
Mutation Made By		Teresa Leone,   Burnham Institute for Medical Research
Strain of Origin		(C57BL/6 x CBA)F1
Expressed Gene		Ppara, peroxisome proliferator activated receptor alpha, mouse, laboratory
Promoter		Ckm, creatine kinase, muscle, mouse, laboratory
Molecular Note		The mouse Ckm (creatine kinase, muscle) promoter drives expression of mouse Ppara (peroxisome proliferator activated receptor alpha) cDNA carrying a C-terminal FLAG tag. This line is a high expressor line. [MGI Ref ID J:129848]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Finck BN; Bernal-Mizrachi C; Han DH; Coleman T; Sambandam N; LaRiviere LL; Holloszy JO; Semenkovich CF; Kelly DP. 2005. A potential link between muscle peroxisome proliferator- activated receptor-alpha signaling and obesity-related diabetes. Cell Metab 1(2):133-44. [PubMed: 16054054]  [MGI Ref ID J:129848]

Additional References

Tg(Ckm-Ppara)HEDpk related

Chau BN; Xin C; Hartner J; Ren S; Castano AP; Linn G; Li J; Tran PT; Kaimal V; Huang X; Chang AN; Li S; Kalra A; Grafals M; Portilla D; MacKenna DA; Orkin SH; Duffield JS. 2012. MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med 4(121):121ra18. [PubMed: 22344686]  [MGI Ref ID J:183786]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

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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.

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