PMID- 15850572
OWN - NLM
STAT- MEDLINE
DCOM- 20050808
LR  - 20231213
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 38
IP  - 5
DP  - 2005 May
TI  - Dysregulation of connexins and inactivation of NFATc1 in the cardiovascular 
      system of Nkx2-5 null mutants.
PG  - 787-98
AB  - In humans, mutations of the gene encoding the transcription factor Nkx2-5 result 
      in the heart in electrical conduction defects and morphological abnormalities. In 
      this organ Nkx2-5 is expressed in both the myocardium and the endocardium. 
      Connexins (Cxs) are gap junction channel proteins that have been shown to be 
      involved in both heart development and cardiac electrical conduction, suggesting 
      a possible correlation between expression of Cxs and Nkx2-5. To evaluate this 
      correlation, the expression of Cxs has been investigated in the cardiovascular 
      system of wild-type and Nkx2-5-/- 9.2 days post-conception (dpc) mouse embryos. 
      The disruption of the Nkx2-5 gene results in the loss of Cx43 in the heart, due 
      in part to the poor development of the ventricular trabecular network, as well as 
      specific downregulation of Cx45 gene expression. In addition, the nuclear 
      translocation of NFATc1 in the endocardial endothelial cells is inhibited in the 
      Nkx2-5-/- embryos. These results indicate for the first time that Nkx2-5 is 
      involved in the transcriptional regulation of the Cx45 gene expression. In the 
      mutant embryos the aorta is collapsed, and the vascular endothelial Cxs, Cx40 and 
      Cx37, are no longer expressed in its posterior region. Poor development of the 
      trabeculae and downregulation of Cx45 may contribute both to failure of the 
      myocardial function and to hemodynamic insufficiency. The latter, in turn, may 
      result in the dysregulation of Cx40 and -37 expressions along the whole length of 
      the aorta. Direct or indirect effects of Nkx2-5 inactivation on the Cx45 gene 
      expression could explain the absence of the endocardial cushions in the heart of 
      Nkx2-5-/- embryos.
FAU - Dupays, Laurent
AU  - Dupays L
AD  - Laboratoire de Genetique et Physiologie du Developpement (UMR CNRS 6545), 
      Institut de Biologie du Developpement de Marseille, Universite de la 
      Mediterranee, 13288 Marseille cedex 9, France.
FAU - Jarry-Guichard, Therese
AU  - Jarry-Guichard T
FAU - Mazurais, David
AU  - Mazurais D
FAU - Calmels, Thierry
AU  - Calmels T
FAU - Izumo, Seigo
AU  - Izumo S
FAU - Gros, Daniel
AU  - Gros D
FAU - Theveniau-Ruissy, Magali
AU  - Theveniau-Ruissy M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Connexin 43)
RN  - 0 (Connexins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeobox Protein Nkx-2.5)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (NFATC1 protein, human)
RN  - 0 (Nfatc1 protein, mouse)
RN  - 0 (Nkx2-5 protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (connexin 45)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cardiovascular Abnormalities/embryology/genetics/physiopathology
MH  - Cardiovascular System/embryology/*metabolism
MH  - Connexin 43/genetics/metabolism
MH  - Connexins/*genetics/metabolism
MH  - DNA/genetics
MH  - DNA-Binding Proteins/*antagonists & inhibitors/metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Homeobox Protein Nkx-2.5
MH  - Homeodomain Proteins/genetics/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Myocardial Contraction/genetics/physiology
MH  - NFATC Transcription Factors
MH  - Nuclear Proteins/*antagonists & inhibitors/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Transcription Factors/*antagonists & inhibitors/*deficiency/genetics/metabolism
MH  - Gap Junction alpha-5 Protein
MH  - Gap Junction alpha-4 Protein
EDAT- 2005/04/27 09:00
MHDA- 2005/08/09 09:00
CRDT- 2005/04/27 09:00
PHST- 2004/12/17 00:00 [received]
PHST- 2005/02/08 00:00 [revised]
PHST- 2005/02/16 00:00 [accepted]
PHST- 2005/04/27 09:00 [pubmed]
PHST- 2005/08/09 09:00 [medline]
PHST- 2005/04/27 09:00 [entrez]
AID - S0022-2828(05)00064-7 [pii]
AID - 10.1016/j.yjmcc.2005.02.021 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2005 May;38(5):787-98. doi: 10.1016/j.yjmcc.2005.02.021.