Although melanoma is a common human disease, there were few animal models in which melanoma developed at high incidence. To date, theXiphophorusfish has been used as a model system to study melanoma formation. Studies on this fish showed the presence of a dominant oncogene,Tu, which encodes a transmembrane, tyrosine kinase of epidermal growth factor receptor type (Wittbrodt et al., Nature, 341:415–421, 1989). Recently, we succeeded in establishing novel transgenic mouse lines in which melanosis and melanocytic tumors developed stepwise by introducing another transmembrane tyrosine kinase oncogene,ret(Iwamoto et al., EMBO J., 10:3167–3175, 1991). In our transgenic mice, high levels of expression of therettransgene induced proliferation and neoplastic transformation of melanin‐producing cells. In addition, crossbreeding experiments between transgenic mice andWvmice showed that theretoncogene can also induce melanogenesis and melanocyte development inWv/W
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