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Cell. 2000 Sep 1;102(5):671-82.

A novel genetic pathway for sudden cardiac death via defects in the transition between ventricular and conduction system cell lineages.

Author information

1
UCSD-Salk Program in Molecular Medicine and the UCSD Institute of Molecular Medicine, University of California, San Diego, La Jolla 92093, USA.

Abstract

HF-1 b, an SP1 -related transcription factor, is preferentially expressed in the cardiac conduction system and ventricular myocytes in the heart. Mice deficient for HF-1 b survive to term and exhibit normal cardiac structure and function but display sudden cardiac death and a complete penetrance of conduction system defects, including spontaneous ventricular tachycardia and a high incidence of AV block. Continuous electrocardiographic recordings clearly documented cardiac arrhythmogenesis as the cause of death. Single-cell analysis revealed an anatomic substrate for arrhythmogenesis, including a decrease and mislocalization of connexins and a marked increase in action potential heterogeneity. Two independent markers reveal defects in the formation of ventricular Purkinje fibers. These studies identify a novel genetic pathway for sudden cardiac death via defects in the transition between ventricular and conduction system cell lineages.

PMID:
11007485
DOI:
10.1016/s0092-8674(00)00089-1
[Indexed for MEDLINE]
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