Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2192170 | Journal of Molecular and Cellular Cardiology | 2006 | 11 Pages |
Abstract
Connexin40 (Cx40) and connexin45 (Cx45) are involved in both cardiac morphogenesis and propagation of electrical activity. We found that Cx40/Cx45 double deficiency (Cx40â/â/Cx45+/â) causes a variety of cardiac defects leading to high mortality during embryonic development and at birth. The majority of Cx40â/â/Cx45+/â embryos and postnatal mice suffered from atrioventricular septal defects. Additional cardiac abnormalities, e.g., ventricular septal defects and abnormal myocardial arrangement, occurred at lower abundance. Electrocardiograms of Cx40â/â/Cx45+/+ and Cx40â/â/Cx45+/â mice revealed prolongation of P-wave, PQ interval and QRS duration compared to controls. Interestingly, in Cx40â/â/Cx45+/â mice, PQ interval and QRS duration were significantly prolonged compared to Cx40â/â/Cx45+/+ mice. We conclude that the gap junctional proteins Cx40 and Cx45 have overlapping and partially compensatory functions with regard to heart morphogenesis and cardiac conduction. Cx45 might be one of the genetic modifiers that can cause variations in the phenotype of connexin40-deficient animals. Our findings may be particularly relevant for understanding molecular factors contributing to human congenital cardiac diseases.
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Authors
Olaf Krüger, Stephan Maxeiner, Jung-Sun Kim, Harold V.M. van Rijen, Jacques M.T. de Bakker, Dominik Eckardt, Klaus Tiemann, Thorsten Lewalter, Alexander Ghanem, Bernd Lüderitz, Klaus Willecke,