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Research Article Free access | 10.1172/JCI119453

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

M H Soonpaa, G Y Koh, L Pajak, S Jing, H Wang, M T Franklin, K K Kim, and L J Field

Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.

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Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.

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Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.

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Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.

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Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.

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Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.

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Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.

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Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.

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Published June 1, 1997 - More info

Published in Volume 99, Issue 11 on June 1, 1997
J Clin Invest. 1997;99(11):2644–2654. https://doi.org/10.1172/JCI119453.
© 1997 The American Society for Clinical Investigation
Published June 1, 1997 - Version history
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Abstract

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.

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