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 Jeffery D. Molkentin,   Children's Hospital Medical Center

Description
Hearts of these targeted mutation mice are hypercontractile, protecting them from heart failure induced by pressure overload. Homozygotes are viable, fertile, and have no overt phenotype. The targeted mutation eliminates expression, as determined by Western blot. This strain may be useful in studies of heart failure.

Development
The exon encoding the ATP-binding region was replaced with a neomycin resistance cassette. A 129-derived embryonic stem (ES) cell line was used to create the mutation. Chimera's were crossed to C57BL/6 and the line was maintained on a mixed C57BL/6 and 129 background by the donating laboratory.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Prkca

010579

STOCK Tg(Myh6-Prkca)1Jmk/J

View Strains carrying other alleles of Prkca     (1 strain)

Phenotype

Phenotype Information

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.

Prkca^tm1Jmk/Prkca^tm1Jmk

        involves: 129

• cardiovascular system phenotype
• *normal* cardiovascular system phenotype
  • heart weight/body weight ratios are not altered in mutants at 16 weeks after myocardial infarction (MI) but ratio is significantly higher in wild-type at this point   (MGI Ref ID J:132098)
  • normal baseline blood pressure and heart rate   (MGI Ref ID J:88510)
• • abnormal cardiac muscle contractility
    • after myocardial infarction (MI), ventricular function is maintained in mutants compared to wild-type; fractional shortening is rescued at most time points evaluated after MI   (MGI Ref ID J:132098)
  • abnormal myocardium layer morphology
    • mutant mice show equivalent infarcted area/area at risk ratio to wild-type after myocardial infarction   (MGI Ref ID J:132098)
  • decreased response of heart to induced stress
    • mice were less susceptible to TAC-induced pressure overload heart failure than wild-type controls   (MGI Ref ID J:88510)
• muscle phenotype
• abnormal cardiac muscle contractility
  • after myocardial infarction (MI), ventricular function is maintained in mutants compared to wild-type; fractional shortening is rescued at most time points evaluated after MI   (MGI Ref ID J:132098)
• homeostasis/metabolism phenotype
• decreased response of heart to induced stress
  • mice were less susceptible to TAC-induced pressure overload heart failure than wild-type controls   (MGI Ref ID J:88510)

View Research Applications

Research Applications

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

Cardiovascular Research
Heart Abnormalities

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Prkcatm1Jmk
Allele Name		targeted mutation 1, Jeffery D Molkentin
Allele Type		Targeted (knock-out)
Common Name(s)		Prkca-;
Mutation Made By		Jeffery Molkentin,   Children's Hospital Medical Center
Strain of Origin		129
ES Cell Line Strain		129
Gene Symbol and Name		Prkca, protein kinase C, alpha
Chromosome		11
Gene Common Name(s)		AAG6; AI875142; PKC-alpha; PKCA; PRKACA; Pkca; expressed sequence AI875142;
Molecular Note		Homologous recombination was used to replace the exon encoding the ATP-binding cassette with a neomycin resistance gene. A lack of protein expression was confirmed by Western blot analysis. [MGI Ref ID J:88510]

Genotyping

Genotyping Information

Genotyping Protocols

Prkca^tm1Jmk STD PCR, Robotic STD
Prkca^tm1Jmk STD PCR, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Braz JC; Gregory K; Pathak A; Zhao W; Sahin B; Klevitsky R; Kimball TF; Lorenz JN; Nairn AC; Liggett SB; Bodi I; Wang S; Schwartz A; Lakatta EG; DePaoli-Roach AA; Robbins J; Hewett TE; Bibb JA; Westfall MV; Kranias EG; Molkentin JD. 2004. PKC-alpha regulates cardiac contractility and propensity toward heart failure. Nat Med 10(3):248-54. [PubMed: 14966518]  [MGI Ref ID J:88510]

Additional References

Prkca^tm1Jmk related

Hambleton M; York A; Sargent MA; Kaiser RA; Lorenz JN; Robbins J; Molkentin JD. 2007. Inducible and myocyte-specific inhibition of PKCalpha enhances cardiac contractility and protects against infarction-induced heart failure. Am J Physiol Heart Circ Physiol 293(6):H3768-71. [PubMed: 17921332]  [MGI Ref ID J:132098]

Hao F; Pysz MA; Curry KJ; Haas KN; Seedhouse SJ; Black AR; Black JD. 2011. Protein Kinase C{alpha} Signaling Regulates Inhibitor of DNA Binding 1 in the Intestinal Epithelium. J Biol Chem 286(20):18104-17. [PubMed: 21454537]  [MGI Ref ID J:172682]

Klein JD; Martin CF; Kent KJ; Sands JM. 2012. Protein kinase C-alpha mediates hypertonicity-stimulated increase in urea transporter phosphorylation in the inner medullary collecting duct. Am J Physiol Renal Physiol 302(9):F1098-103. [PubMed: 22301620]  [MGI Ref ID J:183420]

Konopatskaya O; Gilio K; Harper MT; Zhao Y; Cosemans JM; Karim ZA; Whiteheart SW; Molkentin JD; Verkade P; Watson SP; Heemskerk JW; Poole AW. 2009. PKCalpha regulates platelet granule secretion and thrombus formation in mice. J Clin Invest 119(2):399-407. [PubMed: 19147982]  [MGI Ref ID J:145973]

Liu Q; Chen X; Macdonnell SM; Kranias EG; Lorenz JN; Leitges M; Houser SR; Molkentin JD. 2009. Protein kinase C{alpha}, but not PKC{beta} or PKC{gamma}, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach. Circ Res 105(2):194-200. [PubMed: 19556521]  [MGI Ref ID J:164748]

Navedo MF; Takeda Y; Nieves-Cintron M; Molkentin JD; Santana LF. 2010. Elevated Ca2+ sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells. Am J Physiol Cell Physiol 298(2):C211-20. [PubMed: 19846755]  [MGI Ref ID J:157742]

Nieves-Cintron M; Amberg GC; Navedo MF; Molkentin JD; Santana LF. 2008. The control of Ca2+ influx and NFATc3 signaling in arterial smooth muscle during hypertension. Proc Natl Acad Sci U S A 105(40):15623-8. [PubMed: 18832165]  [MGI Ref ID J:144428]

Thai TL; Blount MA; Klein JD; Sands JM. 2012. Lack of protein kinase C-alpha leads to impaired urine concentrating ability and decreased aquaporin-2 in angiotensin II-induced hypertension. Am J Physiol Renal Physiol 303(1):F37-44. [PubMed: 22492943]  [MGI Ref ID J:187024]

Wang Y; Klein JD; Froehlich O; Sands JM. 2013. Role of protein kinase C-alpha in hypertonicity-stimulated urea permeability in mouse inner medullary collecting ducts. Am J Physiol Renal Physiol 304(2):F233-8. [PubMed: 23097465]  [MGI Ref ID J:192175]

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, heterozygotes or homozygotes may be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	None Available
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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