Cardiomyocyte proliferation in mice expressing α-cardiac myosin heavy chain-SV40 T-antigen transgenes

E. B. Katz, M. E. Steinhelper, J. B. Delcarpio, A. I. Daud, W. C. Claycomb, L. J. Field

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

To determine the proliferative potential of adult ventricular cardiomyocytes, we have generated transgenic mice that express the SV40 large T-antigen oncogene in the heart. A fusion gene comprised of the rat α- cardiac myosin heavy chain promoter and the SV40 early region was used to target oncogene expression to the myocardium. Expression of SV40 large T- antigen was observed in both atrial and ventricular cardiomyocytes in adult transgenic animals. T-antigen expression was associated with hyperplasia in the targeted cells. Immunohistological analysis indicated that the proliferating cells continued to express sarcomeric myosin. Electron microscopic examination demonstrated that cardiomyocytes in various stages of the cell cycle retained ultrastructural characteristics typical of mitotic cardiac muscle cells in vivo. Cardiomyocytes isolated from transgenic tumors were able to proliferate in culture and retained a differentiated phenotype, as evidenced by spontaneous contractile activity. Preliminary studies indicate that these cells can undergo a limited number of passages while retaining this differentiated phenotype. These studies demonstrate that both ventricular and atrial cardiomyocytes from transgenic mice proliferate in response to targeted T-antigen expression.

Original languageEnglish (US)
Pages (from-to)H1867-H1876
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume262
Issue number6 31-6
StatePublished - Jan 1 1992

Keywords

  • cardiac tumorigenesis
  • cardiomyocyte growth
  • transgenic mice

ASJC Scopus subject areas

  • Physiology

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