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

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

Research output: Contribution to journalArticle

175 Citations (Scopus)

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

Fingerprint

Cyclin D1
Cardiac Myocytes
Transgenic Mice
Cyclin D
DNA
Cyclin-Dependent Kinases
Proliferating Cell Nuclear Antigen
Thymidine
Myocardium
Cell Cycle

Keywords

  • Cardiac regeneration
  • Cardiomyocyte terminal differentiation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cyclin D1 overexpression promotes cardiomyocyte DNA synthesis and multinucleation in transgenic mice. / Soonpaa, Mark; Koh, Gou Young; Pajak, Laura; Jing, Shaoliang; Wang, He; Franklin, Michael T.; Kim, Kyung Keun; Field, Loren.

In: Journal of Clinical Investigation, Vol. 99, No. 11, 01.06.1997, p. 2644-2654.

Research output: Contribution to journalArticle

Soonpaa, M, Koh, GY, Pajak, L, Jing, S, Wang, H, Franklin, MT, Kim, KK & Field, L 1997, 'Cyclin D1 overexpression promotes cardiomyocyte DNA synthesis and multinucleation in transgenic mice', Journal of Clinical Investigation, vol. 99, no. 11, pp. 2644-2654.
Soonpaa, Mark ; Koh, Gou Young ; Pajak, Laura ; Jing, Shaoliang ; Wang, He ; Franklin, Michael T. ; Kim, Kyung Keun ; Field, Loren. / Cyclin D1 overexpression promotes cardiomyocyte DNA synthesis and multinucleation in transgenic mice. In: Journal of Clinical Investigation. 1997 ; Vol. 99, No. 11. pp. 2644-2654.
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