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Dilated cardiomyopathy in Erb-b4-deficient ventricular muscle

¹Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Buenos Aires; ²Centro de Investigaciones Cardiovasculares, Universidad de La Plata, La Plata; and ³División de Patología, Universidad Favaloro, Buenos Aires, Argentina; ⁴Medical School, University of California San Diego, and ⁵The Scripps Research Institute, La Jolla; and ⁶Center for Comparative Medicine, University of California Davis, Davis, California

Submitted 18 January 2005 ; accepted in final form 24 April 2005

The neuregulin receptor tyrosine kinase Erb-b4, initially linked to early cardiac development, is shown here to play a critical role in adult cardiac function. In wild-type mice, Erb-b4 protein localized to Z lines and to intercalated disks, suggesting a role in subcellular and intercellular communications of cardiomyocytes. Conditional inactivation of erb-b4 in ventricular muscle cells led to a severe dilated cardiomyopathy, characterized by thinned ventricular walls with eccentric hypertrophy, reduced contractility, and delayed conduction. This cardiac dysfunction may account for premature death in adult erb-b4-knockout mice. This study establishes a critical role for Erb-b4 in the maintenance of normal postnatal cardiac structure and function.

erb-b2; neuregulin; conditional knockout; mouse; heart

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