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PMID: 9169494 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 99 ·No. 11 ·1997-06-01 ·Pages 2644-54

Soonpaa MH, Koh GY, Pajak L, Jing S, Wang H, Franklin MT, Kim KK, Field LJ

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.

MeSH Terms
Animals Cyclin D1 Cyclins/genetics DNA Replication/genetics Flow Cytometry Gene Expression Gene Expression Regulation Giant Cells/pathology Mice Mice, Transgenic Myocardium/pathology,ultrastructure Oncogene Proteins/genetics
Chemicals
Cyclins Oncogene Proteins Cyclin D1
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Soonpaa M H
Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-4800, USA.
Koh G Y
Pajak L
Jing S
Wang H
Franklin M T
Kim K K
Field L J
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119453
Published
1997-06-01
Pages
2644-54
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508110
Subset
IM
Grants
NHLBI NIH HHS · HL-06308 · United States
External Links
PubMed source DOI: 10.1172/JCI119453 PMC Full Text View journal details
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