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Transgenic approaches
Transgenic approaches
The melanin pigment production pathway is unique to melanocytes, and definition of promoters of genes involved in this pathway has allowed for melanocyte-specific transgene expression. The tyrosinase (Tyr) promoter/ enhancer construct has been utilized most often; however, promoter constructs from the dopachrome tautomerase (Dct) gene and microphthalmia transcription factor (Mitf) have also been utilized.2 The first transgenic mouse melanoma model utilized a Tyr promoter/enhancer construct to drive SV40 early region in melanocytes. This model resulted in highly penetrant ocular and cutaneous melanoma.7 Additional models involving transgenic expression of Ret, Hras, Nras, Braf, and HGF were also generated and resulted in highly penetrant melanoma formation. Several of these models utilized transgenes/oncogenes that do not appear to play a major role in human melanoma; however, collectively the models provided the opportunity to study melanoma formation and progression in genetic animal models. The models involving transgenic HGF expression are of note, as it was demonstrated that a single dose of perinatal UV exposure increased melanoma penetrance dramatically and altered the morphological features of resulting melanomas.8 Of note, pagetoid spread of melanoma cells is a common feature in this model and in human melanoma, but is only rarely observed in other mouse melanoma models.