Cardiomyocyte-restricted deletion of connexin43 during mouse development.

D. Eckardt, S. Kirchhoff, J.S. Kim, J. Degen, M. Theis, T. Ott, F. Wiesmann, P.A. Doevendans, W.H. Lamers, J.M. de Bakker, H.V. van Rijen, M.D. Schneider, K. Willecke

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Abstract

Although the gap junction protein Connexin43 (Cx43) is expressed in various cell types during embryonic development, mice with a global inactivation of Cx43 survive until birth but die perinatally due to an obstruction of the right ventricular outflow tract of the heart. To analyze the functional role of Cx43 gap junction channels in cardiomyocytes of the developing and early postnatal heart, we used a MyHC-Cre mice to ablate Cx43 expression selectively in cardiomyocytes during development. We found efficient ablation of Cx43 in cardiomyocytes during embryonic development starting at embryonic day (ED) 9.5 in the ventricular wall. Analyses of cardiac Cx43 protein at birth indicated complete loss of Cx43 expression in cardiomyocytes. All mice homozygously deficient for Cx43 in cardiomyocytes died until postnatal day (PD) 16. Heterozygous inactivation of Cx43 in cardiomyocytes neither altered atrial nor ventricular activation, but homozygous ablation led to changes in ventricular activation, i.e. significant decrease of the QRS-amplitude and prolonged QRS-duration already at PD 4. Cardiac morphology was similar to controls until PD 1, but subtle morphological changes were found in a subgroup of mutant mice at later stages. Besides narrowing of the ventricular outlet region at PD 6, hypertrophy of ventricular myocardium was found at PD 12. Our data indicate that complete inactivation of cardiac Cx43 during development predisposes hearts to develop postnatal morphological alterations, which differ from outflow tract obstructions described for Cx43 null mice. In addition, complete loss of cardiac Cx43 protein during development correlates with slowed ventricular activation at PD 4, impairs viability during development, and leads to death of all mutant mice until PD 16.
Original languageEnglish
Pages (from-to)963-971
JournalJournal of Molecular and Cellular Cardiology
Volume41
Issue number6
DOIs
Publication statusPublished - 1 Jan 2006

Cite this

Eckardt, D., Kirchhoff, S., Kim, J. S., Degen, J., Theis, M., Ott, T., Wiesmann, F., Doevendans, P. A., Lamers, W. H., de Bakker, J. M., van Rijen, H. V., Schneider, M. D., & Willecke, K. (2006). Cardiomyocyte-restricted deletion of connexin43 during mouse development. Journal of Molecular and Cellular Cardiology, 41(6), 963-971. https://doi.org/10.1016/j.yjmcc.2006.07.017