Dilated cardiomyopathy in Erb-b4-deficient ventricular muscle.
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.
García-Rivello
Hernán
H
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, INGEBI, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina.
Taranda
Julián
J
Said
Matilde
M
Cabeza-Meckert
Patricia
P
Vila-Petroff
Martin
M
Scaglione
Jorge
J
Ghio
Sergio
S
Chen
Ju
J
Lai
Cary
C
Laguens
Ruben P
RP
Lloyd
Kent C
KC
Hertig
Cecilia M
CM
D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D066247:Receptor, ErbB-4; D015398:Signal Transduction
D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4