Melanocortin Receptor 1 (Mc1r) signaling is essential for proper pigment production. In its absence, mice are unable to produce eumelanin and display a yellow coat color as seen in lethal yellow mice (A y ). Previous members of my lab have shown that Endothelin Receptor b (EdnrB) signaling can compensate for the lack of Mc1r in pigment production by crossing A y mice with hyperpigmented inducible transgenic mice that over-express the EndrB ligand endothelin 3 in the skin (K5tTA-Edn3). The goal of this study was to determine the mechanism of action for Edn3 signaling in rescuing the coat color phenotype of A y mice. To determine if the darker coat color of K5tTA-Edn3 mice resulted from an increase in the number of follicular melanocytes, I performed immunofluorescence with Tyrp1 antibody. The numbers of follicular melanocytes in transgenic and control mice were not significantly different. I used qRT-PCR to evaluate if the darkened coat color produced by Edn3 overexpression is a result of melanogenic gene regulation in follicular melanocytes. There was at least a two-fold increase in the expression of Mitf, Tyrosinase and Trp1 in the hair follicles of Ay ; K5-Edn3 mice when compared with those of control animals. Additionally, transgenic animals upregulated slc7a11, implying an increased co-production of pheomelanin and eumelanin in these mice. Together these results show that Edn3 should be considered as an important player in melanin production and regulation.
