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

Mark H. Soonpaa, Gou Young Koh, Laura Pajak, Shaoliang Jing, He Wang, Michael T. Franklin, Kyung Keun Kim, Loren J. Field

Research output: Contribution to journalArticle

181 Scopus citations

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 over-expression 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.

Original languageEnglish (US)
Pages (from-to)2644-2654
Number of pages11
JournalJournal of Clinical Investigation
Volume99
Issue number11
DOIs
StatePublished - Jun 1 1997

Keywords

  • Cardiac regeneration
  • Cardiomyocyte terminal differentiation

ASJC Scopus subject areas

  • Medicine(all)

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