Abstract 171: Nkx2-5 Suppresses The Proliferation Of Atrial Cardiomyocytes And Formation Of The Conduction Cells During Cardiac Development
Mutation of human NKX2-5 is linked to atrioventricular conduction abnormalities and atrial septal defects. However, it has been difficult to rigorously examine the primary role of Nkx2-5 during the formation of the atria and cardiac conduction cells due to the concurrent hemodynamic aberration associated with ventricular dysfunction. Here, we examined the role of Nkx2-5 in the formation of the atria and conduction cells. Nkx2-5 was conditionally ablated in the atrial cardiomyocytes using atrial-specific Sln-Cre mouse line. The conditional mutants died shortly after birth, which is earlier and more severe than ventricular-specific knockout of Nkx2-5. While no evidence of ventricular failure was identified, atrial-specific conditional mutants developed congenital heart abnormalities including enlarged foramen ovale and hyperplastic atrial myocardium. Histological analyses revealed that the overproliferation of the atrial myocytes underlies the hyperplastic atrial myocardium prior to the development of the atrial septal enlargement. Moreover, conditional mutants showed massive expansion of SA node, AV node and internodal conduction cells, resulting in atrioventricular blocks that were further exacerbated by catecholamine stimulation. Given that the hemodynamic alteration is minimal during the gestational stages in our model, the misspecification of the conduction cells is not likely due to the alteration of the hemodynamics. Together, these data suggest that Nkx2-5 plays a suppressive role in the proliferation of the atrial cardiomyocytes and the formation of the conduction cells.
- © 2013 by American Heart Association, Inc.