CYCLIN D1 OVEREXPRESSION PROMOTES CARDIOMYOCYTE DNA-SYNTHESIS AND MULTINUCLEATION IN TRANSGENIC MICE

D-type cyclin/cyclin-dependent kinase (CDK) complexes regulate transit through the restriction point of the cell cycle, and thus are require d for the initiation of DNA synthesis. Transgenic mice which overexpre ss cyclin D1 in the heart were produced to determine if D-type cyclin deregulation would alter myocardial development. Cyclin D1 overexpress ion resulted in a concomitant increase in CDK4 levels in the adult myo cardium, as well as modest increases in proliferating cell nuclear ant igen and CDK2 levels. Flow cytometric and morphologic analyses of disp ersed cell preparations indicated that the adult transgenic cardiomyoc ytes had abnormal patterns of multinucleation. Histochemical analyses confirmed a marked increase in number of cardiomyocyte nuclei in secti ons prepared from the transgenic mice as compared with those from cont rol animals. Tritiated thymidine incorporation analyses revealed susta ined cardiomyocyte DNA synthesis in adult transgenic hearts.