Document Detail

The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system.
MedLine Citation:
PMID:  15289437     Owner:  NLM     Status:  MEDLINE    
We report a critical role for the T-box transcription factor Tbx5 in development and maturation of the cardiac conduction system. We find that Tbx5 is expressed throughout the central conduction system, including the atrioventricular bundle and bundle branch conduction system. Tbx5 haploinsufficiency in mice (Tbx5(del/+)), a model of human Holt-Oram syndrome, caused distinct morphological and functional defects in the atrioventricular and bundle branch conduction systems. In the atrioventricular canal, Tbx5 haploinsufficiency caused a maturation failure of conduction system morphology and function. Electrophysiologic testing of Tbx5(del/+) mice suggested a specific atrioventricular node maturation failure. In the ventricular conduction system, Tbx5 haploinsufficiency caused patterning defects of both the left and right ventricular bundle branches, including absence or severe abnormalities of the right bundle branch. Absence of the right bundle branch correlated with right-bundle-branch block by ECG. Deficiencies in the gap junction protein gene connexin 40 (Cx40), a downstream target of Tbx5, did not account for morphologic conduction system defects in Tbx5(del/+) mice. We conclude that Tbx5 is required for Cx40-independent patterning of the cardiac conduction system, and suggest that the electrophysiologic defects in Holt-Oram syndrome reflect a developmental abnormality of the conduction system.
Ivan P G Moskowitz; Anne Pizard; Vickas V Patel; Benoit G Bruneau; Jae B Kim; Sabina Kupershmidt; Dan Roden; Charles I Berul; Christine E Seidman; Jonathan G Seidman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  131     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-03     Completed Date:  2004-10-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  4107-16     Citation Subset:  IM    
Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA.
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MeSH Terms
Connexins / metabolism
Heart / embryology*
Myocardium / metabolism*
T-Box Domain Proteins / deficiency,  genetics,  metabolism*
Reg. No./Substance:
0/Connexins; 0/T-Box Domain Proteins; 0/T-box transcription factor 5

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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