Gene Targets of NKX 2.5 in the Conduction System

University Of California San Francisco, San Francisco CA

Investigators

Abstract

DESCRIPTION (provided by applicant): Mutations in gene encoding the homeobox transcription factor (NKX 2.5) have been found to cause human congenital cardiac disease manifested by structural cardiac changes (VSD, ASD) as well as AV block. Our hypothesis is that NKX 2.5 plays a critical role in regulation of gene expression for development of the cardiac conduction system. Using the Iox-P, Cre technology to develop and further characterize a mouse line with NKX 2.5 knockout, the proposed research plan is to identify the downstream targets of NKX 2.5 knockouts in the AV node and ventricular specialized conduction system utilizing gene expression microarray analyses. Finally, we plan to study the role of specific ion channels (i.e. MinK and HCN-1) in the pathogenesis of arrhythmias in the ventricular restricted knockout mouse model. This will be done by using in-situ hybridization and immunohistochemistry to follow the pattern of expression of these ion channels.