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

Katz, E. B., Steinhelper, M. E., Delcarpio, J. B., Daud, A. I., Claycomb, W. C., Field, L. J. (1992) Cardiomyocyte proliferation in mice expressing alpha-cardiac myosin heavy chain-SV40 T-antigen transgenes. Am J Physiol, 262 (6 Pt 2). H1867-76. ISSN 0002-9513 (Print)0002-9513 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/1377879

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 alpha-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.

Item Type: Paper
Uncontrolled Keywords: Animals Base Sequence Blotting, Western Cell Division Cloning, Molecular *Gene Expression Heart Neoplasms/pathology Immunohistochemistry/methods Mice Mice, Transgenic Molecular Sequence Data Myocardium/*metabolism/pathology/ultrastructure Myosins/chemistry/*genetics Oligonucleotide Probes/genetics Simian virus 40/*genetics Staining and Labeling
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
organs, tissues, organelles, cell types and functions > tissues types and functions > myoblast
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > myosin
CSHL Authors:
Communities: CSHL labs > Stillman lab
Depositing User: Matt Covey
Date Deposited: 01 Oct 2015 20:16
Last Modified: 01 Oct 2015 20:16
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31764

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