Loss of connexin45 causes a cushion defect in early cardiogenesis.
At around embryonic day 9, the primitive heart of a mouse embryo undergoes spectacular alterations within 24 hours. We created mice harboring an nls-lacZ gene in place of connexin45, which encodes the only known gap junction protein in the primitive heart before embryonic day 9, using the Cre-loxP system. Connexin45-deficient mice died of heart failure at around embryonic day 10. They initiated heart contractions, but conduction block appeared within 24 hours after the first contractions. Their cardiac walls displayed an endocardial cushion defect, while the cardiac jelly was present. These abnormalities were caused by impairment of the epithelial-mesenchymal transformation of the cardiac endothelium. Activation of the cardiac endothelium depended on the presence of the connexin45 gap junctions since signaling through Ca(2+)/calcineurin and NF-ATc1 (originally named NF-ATc) was disrupted in the mutant hearts. These results indicate a requirement for gap junction channels during early cardiogenesis and hence implicate connexin45 in congenital heart diseases. http://www. biologists.com/Development/movies/dev4369.html
Kumai
M
M
Department of Developmental Molecular Anatomy, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
Nishii
K
K
Nakamura
K
K
Takeda
N
N
Suzuki
M
M
Shibata
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism; D005314:Embryonic and Fetal Development; D004699:Endocardium; D005260:Female; D020869:Gene Expression Profiling; D006321:Heart / Q000196:embryology* / Q000502:physiology; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors / Q000378:metabolism
D017630:Connexins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C082920:connexin 45; D002118:Calcium