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| The mouse Myh6 (myosin, heavy polypeptide 6, cardiac muscle, alpha) cardiac muscle-specific promoter drives expression of FLAG-tagged Ppara (peroxisome proliferator activated receptor alpha) in this transgenic strain. Hearts of hemizygotes depend on fatty acid for the generation of energy to a significantly greater extent than do hearts of non-transgenic mice and have a substrate utilization profile similar to that of the diabetic heart. Cardiac dysfunction is exhibited by 2 months of age with no imposed stress. This strain may be useful in studies of metabolic alterations associated with diabetic cardiomyopathy. This is the "high expressor" line. | |||||||||||||||||||
- 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
Former Names B6.Cg-Tg(Myh6-Ppara)403-4Dpk/J (Changed: 24-FEB-10 ) 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 N9pN1
Generation DefinitionsDonating Investigator Daniel Kelly, Burnham Institute for Medical Research Description
The mouse Myh6 (myosin, heavy polypeptide 6, cardiac muscle, alpha) cardiac muscle-specific promoter drives expression of FLAG-tagged Ppara (peroxisome proliferator activated receptor alpha) in this transgenic strain. Expression of Ppara is increased approximately 135-fold as compared to wildtype in this line (404-3). Hearts of hemizygotes depend on fatty acid for the generation of energy to a significantly greater extent than do hearts of non-transgenic mice and have a substrate utilization profile similar to that of the diabetic heart. Cardiac dysfunction is exhibited by 2 months of age with no imposed stress. This strain may be useful in studies of metabolic alterations associated with diabetic cardiomyopathy.Development
The mouse Myh6 (myosin, heavy polypeptide 6, cardiac muscle, alpha) 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 at least 9 times to C57BL/6 by the donating laboratory. This is a high expressor line (404-3).
Related Strains
Strains carrying other alleles of Myh6
View Strains carrying other alleles of Myh6 (38 strains)
003580 129S4/SvJae-Pparatm1Gonz/J 012379 B6.Cg-Tg(Ckm-Ppara)HEDpk/J 012382 B6.Cg-Tg(Myh6-Ppara)404-4Dpk/J 008154 B6;129S4-Pparatm1Gonz/J
Phenotype
Phenotype Information
- 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)
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Myh6-Ppara)404-3Dpk/0
involves: C57BL/6 * CBA/J
- cardiovascular system phenotype
- abnormal cardiovascular system physiology
- myocardial uptake of 11C-palmitate is increased, indicating enhanced myocardial uptake of fatty acid (MGI Ref ID J:110580)
- abnormal cardiac cell glucose uptake
- myocardial uptake of 18FDG is lower indicating decreased glucose uptake (MGI Ref ID J:110580)
- cardiomyopathy
- exhibit signatures of diabetic cardiomyopathy including ventricular hypertrophy, activation of gene markers of pathologic hypertrophic growth, and alteration systolic ventricular function (MGI Ref ID J:110580)
- insulin deficient mutants and mutants fed a diet enriched in triglyceride containing long-chain fatty acid develop more severe cardiomyopathy than untreated controls (MGI Ref ID J:81834)
- decreased ventricle muscle contractility
- the posterior wall thickness is increased, LV chamber dilatation, as determined by systolic and diastolic internal diameters, is increased, and fractional shortening is reduced (MGI Ref ID J:110580)
- abnormal myocardial fiber morphology
- exhibit neutral lipid droplet accumulation in cardiac myocytes after a short-term fast (MGI Ref ID J:110580)
- myocardial triacylglycerol levels are higher in fasted mutants than in controls, especially the long-chain fatty acid-containing triacylglycerol (MGI Ref ID J:110580)
- myocyte hypertrophy is seen in 3-month old mutants (MGI Ref ID J:110580)
- cardiac hypertrophy
- exhibit an increase in biventricular weight/body weight ratio (MGI Ref ID J:110580)
- homeostasis/metabolism phenotype
- abnormal lipid level
- exhibit neutral lipid droplet accumulation in cardiac myocytes after a short-term fast (MGI Ref ID J:110580)
- increased fatty acid level
- myocardial triacylglycerol levels are higher in fasted mutants than in controls, specifically long-chain fatty acid-containing triacylglycerol (MGI Ref ID J:110580)
- muscle phenotype
- abnormal cardiac cell glucose uptake
- myocardial uptake of 18FDG is lower indicating decreased glucose uptake (MGI Ref ID J:110580)
- abnormal myocardial fiber morphology
- exhibit neutral lipid droplet accumulation in cardiac myocytes after a short-term fast (MGI Ref ID J:110580)
- myocardial triacylglycerol levels are higher in fasted mutants than in controls, especially the long-chain fatty acid-containing triacylglycerol (MGI Ref ID J:110580)
- myocyte hypertrophy is seen in 3-month old mutants (MGI Ref ID J:110580)
- cardiomyopathy
- exhibit signatures of diabetic cardiomyopathy including ventricular hypertrophy, activation of gene markers of pathologic hypertrophic growth, and alteration systolic ventricular function (MGI Ref ID J:110580)
- insulin deficient mutants and mutants fed a diet enriched in triglyceride containing long-chain fatty acid develop more severe cardiomyopathy than untreated controls (MGI Ref ID J:81834)
- decreased ventricle muscle contractility
- the posterior wall thickness is increased, LV chamber dilatation, as determined by systolic and diastolic internal diameters, is increased, and fractional shortening is reduced (MGI Ref ID J:110580)
This mouse can be used to support research in many areas including:
Cardiovascular Research
Heart Abnormalities
Other
altered fat metabolism
Internal/Organ Research
Heart Abnormalities
Metabolism Research
Lipid Metabolism
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Myh6-Ppara)404-3Dpk | ||
|---|---|---|---|
| Allele Name | transgene insertion 404-3, Daniel P Kelly | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | MHC-PPAR; MHC-PPARalpha; | ||
| Mutation Made By | Teresa Leone, Burnham Institute for Medical Research | ||
| Strain of Origin | (C57BL/6 x CBA/J)F1 | ||
| Expressed Gene | Ppara, peroxisome proliferator activated receptor alpha, mouse, laboratory | ||
| Promoter | Myh6, myosin, heavy polypeptide 6, cardiac muscle, alpha, murine, murine | ||
| General Note | Phenotypic Similarity to Human Syndrome: Diabetes mellitus. Transgenic mice exhibit a cardiac phenotype similar to that seen in diabetes mellitus (J:11050). | ||
| Molecular Note | This transgene consists of a 1.5-kb, NH2-terminal FLAG epitope-tagged Ppara cDNA downstream of the cardiac alpha myosin heavy chain promoter. This line exhibits Ppara protein levels about 135-fold more abundant in cardiac ventricles than in nontransgenics. [MGI Ref ID J:110580] | ||
References
References provided by MGI
Selected Reference(s)
Finck BN; Lehman JJ; Leone TC; Welch MJ; Bennett MJ; Kovacs A; Han X; Gross RW; Kozak R; Lopaschuk GD; Kelly DP. 2002. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 109(1):121-30. [PubMed: 11781357] [MGI Ref ID J:110580]
Additional References
Tg(Myh6-Ppara)404-3Dpk relatedChen W; Xia Y; Zhao X; Wang H; Chen W; Yu M; Li Y; Ye H; Zhang Y. 2012. The critical role of Astragalus polysaccharides for the improvement of PPRAalpha-mediated lipotoxicity in diabetic cardiomyopathy. PLoS One 7(10):e45541. [PubMed: 23049681] [MGI Ref ID J:191956]
Duncan JG; Bharadwaj KG; Fong JL; Mitra R; Sambandam N; Courtois MR; Lavine KJ; Goldberg IJ; Kelly DP. 2010. Rescue of cardiomyopathy in peroxisome proliferator-activated receptor-alpha transgenic mice by deletion of lipoprotein lipase identifies sources of cardiac lipids and peroxisome proliferator-activated receptor-alpha activators. Circulation 121(3):426-35. [PubMed: 20065164] [MGI Ref ID J:168445]
Duncan JG; Fong JL; Medeiros DM; Finck BN; Kelly DP. 2007. Insulin-resistant heart exhibits a mitochondrial biogenic response driven by the peroxisome proliferator-activated receptor-alpha/PGC-1alpha gene regulatory pathway. Circulation 115(7):909-17. [PubMed: 17261654] [MGI Ref ID J:130544]
Finck BN; Han X; Courtois M; Aimond F; Nerbonne JM; Kovacs A; Gross RW; Kelly DP. 2003. A critical role for PPARalpha -mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation by dietary fat content. Proc Natl Acad Sci U S A 100(3):1226-31. [PubMed: 12552126] [MGI Ref ID J:81834]
Harris IS; Treskov I; Rowley MW; Heximer S; Kaltenbronn K; Finck BN; Gross RW; Kelly DP; Blumer KJ; Muslin AJ. 2004. G-protein signaling participates in the development of diabetic cardiomyopathy. Diabetes 53(12):3082-90. [PubMed: 15561937] [MGI Ref ID J:132894]
Marionneau C; Aimond F; Brunet S; Niwa N; Finck B; Kelly DP; Nerbonne JM. 2008. PPARalpha-mediated remodeling of repolarizing voltage-gated K+ (Kv) channels in a mouse model of metabolic cardiomyopathy. J Mol Cell Cardiol 44(6):1002-15. [PubMed: 18482733] [MGI Ref ID J:137542]
Oka S; Alcendor R; Zhai P; Park JY; Shao D; Cho J; Yamamoto T; Tian B; Sadoshima J. 2011. PPARalpha-Sirt1 complex mediates cardiac hypertrophy and failure through suppression of the ERR transcriptional pathway. Cell Metab 14(5):598-611. [PubMed: 22055503] [MGI Ref ID J:179686]
Yang J; Sambandam N; Han X; Gross RW; Courtois M; Kovacs A; Febbraio M; Finck BN; Kelly DP. 2007. CD36 deficiency rescues lipotoxic cardiomyopathy. Circ Res 100(8):1208-17. [PubMed: 17363697] [MGI Ref ID J:135377]
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 maintained as a live colony, hemizygotes may be bred.
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* $2250.00 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 |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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.
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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.Ordering Information
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