Transgenic mouse models for tumors of melanocytes and retinal pigment epithelium

Cutaneous and ocular melanomas are due to malignant transformation of neura l crest-derived melanocytes. The rising incidence of this tumor in humans h as stimulated experiments to devise suitable mouse models. In the past year s, transgenic mouse lines have been generated using different oncogenes - H a-ras, SV40 T antigen (Tag), ret - which develop benign lesions of melanocy tes, melanoma, and/or eye tumors. Pigment cell tumors in humans, although r ather rare, can also develop from the retinal pigment epithelium (RPE), a c ell layer of neuroectodermal origin. We, therefore, established transgenic models for this ocular tumor. Regulated by the promoter of tyrosinase-relat ed protein-1 (TRP-1), two oncogenes, ret and SV40 Tag, were targeted to the developing RPE in transgenic mice. The TRP-1/ret transgenic mice displayed microphthalmia and benign tumors of the RPE. Expression of SV40 T antigen (TRP-1/Tag) led to malignant tumors, which were invasive and metastasized t o inguinal lymph node and spleen.