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 journalArticle

22 Scopus citations

Abstract

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
Volume280
Issue number2
DOIs
StatePublished - Oct 1 2004

Keywords

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

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    Jay, P. Y., Harris, B. S., Buerger, A., Rozhitskaya, O., Maguire, C. T., Barbosky, L. A., Mccusty, E., Berul, C. I., O'Brien, T. X., Gourdie, R. G., & Izumo, S. (2004). Function follows form: Cardiac conduction system defects in Nkx2-5 mutation. Anatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology, 280(2), 966-972. https://doi.org/10.1002/ar.a.20102