MALIGNANT-MELANOMA IN TRANSGENIC MICE

Ocular and cutaneous melanomas arose in new inbred lines of transgenic mice having an integrated recombinant gene comprised of the tyrosinase promoter, expressed in pigment cells, and the simian virus 40 early-region transforming sequences. The tumors were hypomelanotic and were histopathologically similar to corresponding human melanomas. Eye melanomas often originated at a young age, chiefly from the retinal pigment epithelium, also from the choroid, and rarely from the ciliary body. The eye tumors grew aggressively, were highly invasive, and metastasized to local and distant sites. The earliest formation of these tumors was associated with higher copy numbers of the transgene; mice of different single-copy lines varied greatly in age of onset and frequency of eye tumors. Coat pigmentation was reduced in almost all lines, to various extents. Primary skin melanomas arose later and less frequently than eye melanomas. Hence they were at early stages and of unknown long-range incidence in this investigation, in which autopsies covered the first half-year of life. For both ocular and cutaneous melanomas, the transgenic mice offer numerous possibilities for experimental study of mechanisms underlying formation and spread of melanomas.