| First Author | Mohamed RM | Year | 2016 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 310 |
| Issue | 11 | Pages | H1808-15 |
| PubMed ID | 27106044 | Mgi Jnum | J:234791 |
| Mgi Id | MGI:5790886 | Doi | 10.1152/ajpheart.00771.2015 |
| Citation | Mohamed RM, et al. (2016) GSK-3beta heterozygous knockout is cardioprotective in a knockin mouse model of familial dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 310(11):H1808-15 |
| abstractText | Glycogen synthase kinase-3beta (GSK-3beta) plays a central role in both cardiac physiology and pathology. Herein we want to clarify the role of GSK-3beta in familial dilated cardiomyopathy. We generated a mouse model carrying a heterozygous knockout mutation of GSK-3beta (GSK-3beta(+/-) KO), together with a DeltaK210 knockin mutation in cardiac troponin T (DeltaK210 cTnT KI), which was proved to be one of the genetic causes of familial dilated cardiomyopathy (DCM). GSK-3beta(+/-) KO prevented the slow and rapid deterioration in left ventricular systolic function accompanying heart failure (HF) in DCM mice with heterozygous and homozygous DeltaK210 cTnT KI mutations, respectively. GSK-3beta(+/-) KO also prevented cardiac enlargement, myocardial fibrosis, and cardiomyocyte apoptosis and markedly reduced the expression of cardiac beta-myosin heavy chain isoform, indicative of HF, in DCM mice with homozygous DeltaK210 cTnT KI mutation. GSK-3beta(+/-) KO also extended the life span of these DCM mice. This study suggests that the inhibition of GSK-3beta is cardioprotective in familial DCM associated with DeltaK210 cTnT mutation. |
