CONDUCTION SYSTEM DEFECTS IN THE VENTRICULAR SPECIFIC ERBB4 KNOCKOUT MOUSE

BUITRAGO-EMANUEL E, TARELLI R, MALVICINI M, HERTIG CM.

Misiones

Congreso; LV Reunion Anual de la Sociedad Argentina de Investigación Bioquimica; 2004

Sociedad Argentina de Investigación Bioquímica

Conditional inactivation of erbB4 in ventricular muscle induces cardiac dilation and conduction abnormalities, leading to heart failure in adult mice (erbB4 CKO). Electrocardiographic recordings of erbB4 CKO showed widened QRS complex and prolonged QT, which are usual conduction defects affecting individuals with diverse symptoms ranging from arrythmias to sudden death. We investigated the role of erbB4 in the formation of the conduction system by monitoring the cellular localization and expression of Connexin-40 (Cx40), the most accepted developmental marker of the His bundle-Purkinje fiber system, and of Desmin. The expression of Cx40 and Desmin were respectively reduced to 50% and 70% in erbB4 CKO as measured in Western blots. Cx40 protein was observed by immunohistochemistry in a cluster of smaller cells compared to wildtype embryos. Postnatal analysis showed a lack of targeting of Cx40 to intercalated discs, instead Cx40 was detected along the cardiomyocyte membrane. This result suggests a delayed or miss-differentiation of cells forming the His- Purkinje fiber system. We also examined changes in the expression of specific ion channels that may be underlying the observed conduction defects. We speculate that erbB4 plays a morphogenetic role, where it is required for normal differentiation of trabecular myocytes into structures of the conduction system.