Author/Authors :
Vân T.B Nguyê?-Trân، نويسنده , , Steven W. Kubalak، نويسنده , , Susumu Minamisawa، نويسنده , , Céline Fiset، نويسنده , , Kai C. Wollert، نويسنده , , Anne B Brown، نويسنده , , Pilar Ruiz-Lozano، نويسنده , , Stéphanie Barrere-Lemaire، نويسنده , , Richard Kondo، نويسنده , , Lisa W Norman، نويسنده , , Robert G. Gourdie، نويسنده , , Marc M Rahme، نويسنده , , Gregory K. Feld، نويسنده , , Robert B Clark، نويسنده , , Wayne R Giles، نويسنده , , Kenneth R. Chien، نويسنده ,
Abstract :
HF-1b, an SP1-related transcription factor, is preferentially expressed in the cardiac conduction system and ventricular myocytes in the heart. Mice deficient for HF-1b 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.
