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rdf:type |
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lifeskim:mentions |
umls-concept:C0151517,
umls-concept:C0152021,
umls-concept:C0181586,
umls-concept:C0205329,
umls-concept:C0878544,
umls-concept:C1413784,
umls-concept:C1517945,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1881379,
umls-concept:C2339371,
umls-concept:C2348235
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pubmed:issue |
3
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pubmed:dateCreated |
2004-4-27
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0092-8674
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pubmed:author |
pubmed-author:AmandTara StTS,
pubmed-author:BensonD WoodrowDW,
pubmed-author:ChenHanyingH,
pubmed-author:ChienKenneth RKR,
pubmed-author:ClarkBobB,
pubmed-author:EvansSylvia MSM,
pubmed-author:FeramiscoJames RJR,
pubmed-author:GilesWayneW,
pubmed-author:HoSiew YenSY,
pubmed-author:KondoRichardR,
pubmed-author:LuJonathan TJT,
pubmed-author:PashmforoushMohammadM,
pubmed-author:PradervandSylvainS,
pubmed-author:ShouWeinianW,
pubmed-author:SilberbachMichaelM
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
373-86
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pubmed:dateRevised |
2011-9-22
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pubmed:meshHeading |
pubmed-meshheading:15109497-Acetylcholinesterase,
pubmed-meshheading:15109497-Aging,
pubmed-meshheading:15109497-Animals,
pubmed-meshheading:15109497-Animals, Newborn,
pubmed-meshheading:15109497-Cardiomyopathies,
pubmed-meshheading:15109497-Cell Lineage,
pubmed-meshheading:15109497-Electric Conductivity,
pubmed-meshheading:15109497-Electrocardiography,
pubmed-meshheading:15109497-Gene Deletion,
pubmed-meshheading:15109497-Gene Expression,
pubmed-meshheading:15109497-Gene Expression Profiling,
pubmed-meshheading:15109497-Gene Targeting,
pubmed-meshheading:15109497-Genes, Reporter,
pubmed-meshheading:15109497-Heart Block,
pubmed-meshheading:15109497-Heart Defects, Congenital,
pubmed-meshheading:15109497-Heart Ventricles,
pubmed-meshheading:15109497-Homeodomain Proteins,
pubmed-meshheading:15109497-Humans,
pubmed-meshheading:15109497-Mice,
pubmed-meshheading:15109497-Mice, Knockout,
pubmed-meshheading:15109497-Myocytes, Cardiac,
pubmed-meshheading:15109497-Reproducibility of Results,
pubmed-meshheading:15109497-Time Factors,
pubmed-meshheading:15109497-Transcription, Genetic,
pubmed-meshheading:15109497-Transcription Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block.
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pubmed:affiliation |
UCSD Institute of Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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