Cyclin D1 overexpression promotes cardiomyocyte DNA synthesis and multinucleation in transgenic mice

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D-type cyclin/cyclin-dependent kinase (CDK) complexes regulate transit through the restriction point of the cell cycle, and thus are required for the initiation of DNA synthesis. Transgenic mice which overexpress cyclin D1 in the heart were produced to determine if D-type cyclin deregulation would alter myocardial development. Cyclin D1 overexpression resulted in a concomitant increase in CDK4 levels in the adult myocardium, as well as modest increases in proliferating cell nuclear antigen and CDK2 levels. Flow cytometric and morphologic analyses of dispersed cell preparations indicated that the adult transgenic cardiomyocytes had abnormal patterns of multinucleation. Histochemical analyses confirmed a marked increase in number of cardiomyocyte nuclei in sections prepared from the transgenic mice as compared with those from control animals. Tritiated thymidine incorporation analyses revealed sustained cardiomyocyte DNA synthesis in adult transgenic hearts.
Publisher
ROCKEFELLER UNIV PRESS
Issue Date
1997-06
Language
English
Article Type
Article
Keywords

C-MYC PROTOONCOGENE; HEAVY-CHAIN GENES; RETINOBLASTOMA PROTEIN; CELL-CYCLE; CARDIAC DEVELOPMENT; EXPRESSION; GROWTH; RAT; CLONING; PHASE

Citation

JOURNAL OF CLINICAL INVESTIGATION, v.99, no.11, pp.2644 - 2654

ISSN
0021-9738
DOI
10.1172/JCI119453
URI
http://hdl.handle.net/10203/77483
Appears in Collection
MSE-Journal Papers(저널논문)
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