Function follows form: Cardiac conduction system defects in Nkx2-5 mutation

Patrick Y. Jay, Brett S. Harris, Antje Buerger, Olga Rozhitskaya, Colin T. Maguire, Laura A. Barbosky, Ellen Mccusty, Charles I. Berul, Terrence X. O'Brien, Robert G. Gourdie, Seigo Izumo

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Mutations of Nkx2-5 cause congenital heart disease and atrioventricular block in man. The altered expression of an electrophysiologic protein regulated by Nkx2-5 was originally presumed to cause the conduction defect, but when no such protein was found, an alternative hypothesis was considered. In pediatric patients, the association of certain cardiac malformations with congenital atrioventricular block suggests that errors in specific developmental pathways could cause both an anatomic and a physiologic defect. We therefore hypothesized that Nkx2-5 insufficiency perturbs the conduction system during development, which in turn manifests as a postnatal conduction defect. Experimental results from Nkx2-5 knockout mouse models support the developmental hypothesis. Hypoplasia of the atrioventricular node, His bundle, and Purkinje system can explain in whole or in part specific conduction and electrophysiologic defects present in Nkx2-5 haploinsufficiency.

Original languageEnglish
Pages (from-to)966-972
Number of pages7
JournalAnatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology
Issue number2
StatePublished - Oct 2004


  • Cardiac electrophysiology
  • Conduction system development
  • Mouse model
  • Nkx2-5


Dive into the research topics of 'Function follows form: Cardiac conduction system defects in Nkx2-5 mutation'. Together they form a unique fingerprint.

Cite this