Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2
- 26 November 2002
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 99 (25), 16197-16202
- https://doi.org/10.1073/pnas.252648999
Abstract
Ventricular septal defects are common in human infants, but the genetic programs that control ventricular septation are poorly understood. Here we report that mice with a targeted disruption of the cardiovascular basic helix–loop–helix factor (CHF)1/Hey2 gene show isolated ventricular septal defects. These defects result primarily in failure to thrive. Mice often succumbed within the first 3 wk after birth and showed pulmonary and liver congestion. The penetrance of this phenotype varied, depending on genetic background, suggesting the presence of modifier genes. Expression patterns of other cardiac-specific genes were not affected. Of the few animals on a mixed genetic background that survived to adulthood, most developed a cardiomyopathy but did not have ventricular septal defects. Our results indicate that CHF1 plays an important role in regulation of ventricular septation in mammalian heart development and is important for normal myocardial contractility. These mice provide a useful model for the study of the ontogeny and natural history of ventricular septal defects and cardiomyopathy.Keywords
This publication has 48 references indexed in Scilit:
- Mouse gridlock: No Aortic Coarctation or Deficiency, but Fatal Cardiac Defects in Hey2 −/− MiceCurrent Biology, 2002
- Gridlock signalling pathway fashions the first embryonic arteryNature, 2001
- Early Postnatal Cardiac Changes and Premature Death in Transgenic Mice Overexpressing a Mutant Form of Serum Response FactorPublished by Elsevier BV ,2001
- Regulation of Myogenic Terminal Differentiation by the Hairy-related Transcription Factor CHF2Published by Elsevier BV ,2001
- Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathwaysJCI Insight, 1999
- Identification and Expression of a Novel Family of bHLH cDNAs Related to Drosophila Hairy and Enhancer of SplitBiochemical and Biophysical Research Communications, 1999
- Neonatal cardiomyopathy in mice homozygous for the Arg403Gln mutation in the α cardiac myosin heavy chain geneJCI Insight, 1999
- Null Mutation in the Desmin Gene Gives Rise to a CardiomyopathyJournal of Molecular and Cellular Cardiology, 1997
- RXR alpha deficiency confers genetic susceptibility for aortic sac, conotruncal, atrioventricular cushion, and ventricular muscle defects in mice.JCI Insight, 1996
- A Subclass of bHLH Proteins Required for Cardiac MorphogenesisScience, 1995