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Am J Physiol Heart Circ Physiol (April 29, 2005). doi:10.1152/ajpheart.00048.2005
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00048.2005v1
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Submitted on January 18, 2005
Accepted on April 24, 2005

Dilated cardiomyopathy in ErbB4-deficient ventricular muscle

Hernan Garcia-Rivello1, Julian Taranda1, Matilde Said2, Patricia Cabeza-Meckert3, Martin Vila-Petroff2, Jorge Scaglione1, Sergio Ghio1, Ju Chen4, Cary Lai5, Ruben P Laguens3, Kent C Lloyd6, and Cecilia M Hertig1*

1 Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular, INGEBI, Buenos Aires, Argentina
2 Centro de Investigaciones Cardiovasculares, La Plata, Argentina
3 Pathology Department, Universidad Favaloro, Buenos Aires, Argentina
4 UCSD, Institute of Molecular Medicine, California, USA
5 The Scripps Research Institute, La Jolla, California, USA
6 Center for Comparative Medicine, University of California Davis, California, USA

* To whom correspondence should be addressed. E-mail: chertig{at}dna.uba.ar.

The neuregulin receptor tyrosine kinase erbB4, initially linked to early cardiac development, is shown here to play a critical role in adult cardiac function. In wild type mice, erbB4 protein localized to Z-lines and to intercalated discs, suggesting a role in subcellular and intercellular communications of cardiac myocytes. Conditional inactivation of erbB4 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 erbB4 knockout mice. This study establishes a critical role for erbB4 in the maintenance of normal postnatal cardiac structure and function.




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