Highly pigmented Tg(Grm1) mouse melanoma develops non-pigmented melanoma cells in distant metastases.

Murine model systems are critically required tools for the investigation of unknown mechanisms of melanoma development and metastasis and for developing more efficient therapies. The Tg(Grm1)EPv melanoma mouse model is characterized by spontaneous development of pigmented cutaneous melanomas at hairless skin regions, with a short latency and 100% penetrance. Local metastasis was described in initial analyses; however, melanoma cells were not observed in distant organs. Here, we demonstrate that the established Tg(Grm1)EPv melanoma mouse model exhibits more extensive metastasis into distant organs than previously described. Disseminated cells undergo phenotypic changes, as we observed high numbers of non-pigmented Grm1-expressing melanoma cells within distant organs. As such changes during metastasis are common in human melanoma, our findings demonstrate that this mouse model represents an even more useful tool to study unknown mechanisms of metastasis in human melanoma than previously assumed.