| First Author | Schaeffer PJ | Year | 2009 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 297 |
| Issue | 4 | Pages | H1263-73 |
| PubMed ID | 19700627 | Mgi Jnum | J:154326 |
| Mgi Id | MGI:4367652 | Doi | 10.1152/ajpheart.00152.2009 |
| Citation | Schaeffer PJ, et al. (2009) Impaired contractile function and calcium handling in hearts of cardiac-specific calcineurin b1-deficient mice. Am J Physiol Heart Circ Physiol 297(4):H1263-73 |
| abstractText | To define the necessity of calcineurin (Cn) signaling for cardiac maturation and function, the postnatal phenotype of mice with cardiac-specific targeted ablation of the Cn B1 regulatory subunit (Ppp3r1) gene (csCnb1(-/-) mice) was characterized. csCnb1(-/-) mice develop a lethal cardiomyopathy, characterized by impaired postnatal growth of the heart and combined systolic and diastolic relaxation abnormalities, despite a lack of structural derangements. Notably, the csCnb1(-/-) hearts did not exhibit diastolic dilatation, despite the severe functional phenotype. Myocytes isolated from the mutant mice exhibited reduced rates of contraction/relaxation and abnormalities in calcium transients, consistent with altered sarcoplasmic reticulum loading. Levels of sarco(endo) plasmic reticulum Ca-ATPase 2a (Atp2a2) and phospholamban were normal, but phospholamban phosphorylation was markedly reduced at Ser(16) and Thr(17). In addition, levels of the Na/Ca exchanger (Slc8a1) were modestly reduced. These results define a novel mouse model of cardiac-specific Cn deficiency and demonstrate novel links between Cn signaling, postnatal growth of the heart, pathological ventricular remodeling, and excitation-contraction coupling. |
