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

摘要: The ErbB2 (Her2) proto-oncogene encodes a receptor tyrosine kinase, which is frequently amplified and overexpressed in human tumors. provides the target for novel effective antibody-based therapy (Trastuzumab/Herceptin) used treatment of mammary carcinomas. However, cardiomyopathies develop proportion patients treated with Trastuzumab, incidence such complications increased by combination standard chemotherapy. Gene ablation studies have previously demonstrated that receptor, together its coreceptor ErbB4 ligand Neuregulin-1, are essential normal development heart ventricle. We use here Cre-loxP technology to mutate specifically ventricular cardiomyocytes. Conditional mutant mice severe dilated cardiomyopathy, signs cardiac dysfunction generally appearing second postnatal month. infer signaling from enriched T-tubules cardiomyocytes, crucial adult function. provide model cardiomyopathy. In particular, they will allow rigorous assessment role insight into molecular mechanisms underlie adverse effects anti-ErbB2 antibodies.