Abstract 14952: CHF1/Hey2 Regulates the Formation of the Cardiac Conduction System
Regulation of cardiac conduction system development is a complex process that is not fully understood. CHF1/Hey2 is a bHLH transcription factor involved in mouse cardiac development and in particular its absence leads to abnormal cardiac ventricular myocyte differentiation manifested by ectopic expression of atrial genes in the compact ventricular myocardium. The His-Purkinje system has an increased level of atrial natriuretic factor expression compared to the surrounding ventricular myocardium and is thought to arise from the surrounding myocardium. Therefore we hypothesized that the absence of CHF1/Hey2 would result in altered development of the cardiac conduction system (CCS) and an increased propensity for arrhythmias. To test this hypothesis we crossed mice expressing beta-galactosidase throughout the CCS with mice lacking CHF1/Hey2 in the myocardium (cKO) followed by X-gal staining of the CCS. Here we demonstrate with histology and optical projection tomography that CHF1 cKO mice have an increased amount of beta-galactosidase staining tissue suggestive of excessive CCS formation compared to both CHF1Flox/Flox and CHF1+/Flox, alphaMHC-Cre+/- controls. To examine the electrophysiologic consequences of this excessive CCS tissue, we performed continuous ambulatory telemetry on adult mice. We did not find any difference in the PR, QRS, or QT intervals comparing cKO and CHF1Flox/Flox controls. However in preliminary telemetry analysis we observed a narrow complex tachyarrhythmia without an identifiable p wave in 1 of 5 cKO mice whereas 0 of 3 CHF1Flox/Flox control mice demonstrated this finding. We conclude that CHF1/Hey2 regulates the development of the cardiac conduction system most likely through a cell autonomous effect on cardiac myocyte differentiation.
- © 2012 by American Heart Association, Inc.