| First Author | Liu Y | Year | 2011 |
| Journal | Assay Drug Dev Technol | Volume | 9 |
| Issue | 6 | Pages | 620-7 |
| PubMed ID | 22087651 | Mgi Jnum | J:198903 |
| Mgi Id | MGI:5499717 | Doi | 10.1089/adt.2011.0411 |
| Citation | Liu Y, et al. (2011) Transgenic analysis of the role of FKBP12.6 in cardiac function and intracellular calcium release. Assay Drug Dev Technol 9(6):620-7 |
| abstractText | FK506 binding protein12.6 (FKBP12.6) binds to the Ca(2+) release channel ryanodine receptor (RyR2) in cardiomyocytes and stabilizes RyR2 to prevent premature sarcoplasmic reticulum Ca(2+) release. Previously, two different mouse strains deficient in FKBP12.6 were reported to have different abnormal cardiac phenotypes. The first mutant strain displayed sex-dependent cardiac hypertrophy, while the second displayed exercise-induced cardiac arrhythmia and sudden death. In this study, we tested whether FKBP12.6-deficient mice that display hypertrophic hearts can develop exercise-induced cardiac sudden death and whether the hypertrophic heart is a direct consequence of abnormal calcium handling in mutant cardiomyocytes. Our data show that FKBP12.6-deficient mice with cardiac hypertrophy do not display exercise-induced arrhythmia and/or sudden cardiac death. To investigate the role of FKBP12.6 overexpression for cardiac function and cardiomyocyte calcium release, we generated a transgenic mouse line with cardiac specific overexpression of FKBP12.6 using alpha-myosin heavy chain (alphaMHC) promoter. MHC-FKBP12.6 mice displayed normal cardiac development and function. We demonstrated that MHC-FKBP12.6 mice are able to rescue abnormal cardiac hypertrophy and abnormal calcium release in FKBP12.6-deficient mice. |
