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Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy

Item Type:Article
Title:Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy
Creators Name:Oezcelik, C. and Erdmann, B. and Pilz, B. and Wettschureck, N. and Britsch, S. and Huebner, N. and Chien, K.R. and Birchmeier, C. and Garratt, A.N.
Abstract:The ErbB2 (Her2) proto-oncogene encodes a receptor tyrosine kinase, which is frequently amplified and overexpressed in human tumors. ErbB2 provides the target for a novel and effective antibody-based therapy (Trastuzumab/Herceptin) used for the treatment of mammary carcinomas. However, cardiomyopathies develop in a proportion of patients treated with Trastuzumab, and the incidence of such complications is increased by combination with standard chemotherapy. Gene ablation studies have previously demonstrated that the ErbB2 receptor, together with its coreceptor ErbB4 and the ligand Neuregulin-1, are essential for normal development of the heart ventricle. We use here Cre-/oxP technology to mutate ErbB2 specifically in ventricular cardiomyocytes. Conditional mutant mice develop a severe dilated cardiomyopathy, with signs of cardiac dysfunction generally appearing by the second postnatal month. We infer that signaling from the ErbB2 receptor, which is enriched in T-tubules in cardiomyocytes, is crucial for adult heart function. Conditional ErbB2 mutant mice provide a model of dilated cardiomyopathy. In particular, they will allow a rigorous assessment of the role of ErbB2 in the heart and provide insight into the molecular mechanisms that underlie the adverse effects of anti-ErbB2 antibodies.
Keywords:Dilated Cardiomyopathy, ErbB-2 Receptor, Mutant Strains Mice, Mutation, Myocardium, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:8880-8885
Date:25 June 2002
Official Publication:https://doi.org/10.1073/pnas.122249299
PubMed:View item in PubMed

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