Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block.

Details

Serval ID
serval:BIB_BDC135519797
Type
Article: article from journal or magazin.
Collection
Publications
Title
Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block.
Journal
Cell
Author(s)
Pashmforoush M., Lu J.T., Chen H., Amand T.S., Kondo R., Pradervand S., Evans S.M., Clark B., Feramisco J.R., Giles W., Ho S.Y., Benson D.W., Silberbach M., Shou W., Chien K.R.
ISSN
0092-8674 (Print)
ISSN-L
0092-8674
Publication state
Published
Issued date
30/04/2004
Peer-reviewed
Oui
Volume
117
Number
3
Pages
373-386
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
Human mutations in Nkx2-5 lead to progressive cardiomyopathy and conduction defects via unknown mechanisms. To define these pathways, we generated mice with a ventricular-restricted knockout of Nkx2-5, which display no structural defects but have progressive complete heart block, and massive trabecular muscle overgrowth found in some patients with Nkx2-5 mutations. At birth, mutant mice display a hypoplastic atrioventricular (AV) node and then develop selective dropout of these conduction cells. Transcriptional profiling uncovered the aberrant expression of a unique panel of atrial and conduction system-restricted target genes, as well as the ectopic, high level BMP-10 expression in the adult ventricular myocardium. Further, BMP-10 is shown to be necessary and sufficient for a major component of the ventricular muscle defects. Accordingly, loss of ventricular muscle cell lineage specification into trabecular and conduction system myocytes is a new mechanistic pathway for progressive cardiomyopathy and conduction defects in congenital heart disease.
Keywords
Acetylcholinesterase/metabolism, Aging, Animals, Animals, Newborn, Cardiomyopathies/genetics, Cardiomyopathies/pathology, Cell Lineage, Electric Conductivity, Electrocardiography, Gene Deletion, Gene Expression, Gene Expression Profiling, Gene Targeting, Genes, Reporter, Heart Block/embryology, Heart Block/genetics, Heart Block/physiopathology, Heart Defects, Congenital/complications, Heart Defects, Congenital/physiopathology, Heart Ventricles/cytology, Homeobox Protein Nkx-2.5, Homeodomain Proteins/genetics, Homeodomain Proteins/metabolism, Humans, Mice, Mice, Knockout, Myocytes, Cardiac/cytology, Reproducibility of Results, Time Factors, Transcription Factors/deficiency, Transcription Factors/genetics, Transcription Factors/metabolism, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
18/12/2014 16:35
Last modification date
25/03/2024 17:35
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