Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mech Dev. 2004 Jun;121(6):559-72.

Ablation of the CLP-1 gene leads to down-regulation of the HAND1 gene and abnormality of the left ventricle of the heart and fetal death.

Author information

  • 1Department of Anatomy and Cell Biology, Center for Cardiovascular and Muscle Research, State University of New York, Health Science Center at Brooklyn, Box 5, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.

Abstract

We have recently reported that cardiac lineage protein-1 (CLP-1), a nuclear protein with an acidic region that constitutes a potential protein-protein interaction domain, regulates transcription of the cardiac myosin light chain-2v (MLC-2v) gene promoter in a manner consistent with its being a transcriptional co-activator or regulator. To test the postulate that CLP-1 is a regulator of cardiac genes we ablated the CLP-1 gene in mice. Past embryonic day (E)16.5, CLP-1 null alleles did not show Mendelian inheritance suggesting that absence of CLP-1 was lethal in late fetal stages. CLP-1 (-/-) fetal hearts exhibited a reduced left ventricular chamber with thickened myocardial walls, features suggestive of cardiac hypertrophy. Electron microscopic analysis of E16.5 CLP-1 (-/-) ventricular myocardium showed a marked decline in cell density and altered nuclear and myofibril morphologies similar to that seen in animal models of hypertrophic heart. Analysis of contractile and non-contractile protein genes known to be re-expressed during cardiac hypertrophy showed them to have higher expression levels in CLP-1 (-/-) hearts thereby confirming the hypertrophic phenotype at the molecular level. Analysis of cardiac development genes showed that expression of the HAND1 transcription factor, a gene involved in patterning of the heart tube and down-regulated in hypertrophic hearts, was also significantly reduced in CLP-1 (-/-) fetal hearts. CLP-1 and HAND1 have similar expression patterns in the developing heart ventricles. These data suggest that CLP-1 and the HAND transcription factors may be part of a genetic program critical to proper heart development, perturbation of which can lead to cardiomyopathy.

Copyright 2004 Elsevier Ireland Ltd.

PMID:
15172687
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Write to the Help Desk