Excess Tyrosine rescues the reduced activity of the proliferation and differentiation of cultured recessive yellow melanocytes of neonatal mouse epidermis

The mouse recessive yellow (Mc1re) is a loss-of-function mutation in the receptor for arpha-melanocyte-stimulating hormone, melanocortin receptor 1 (Mc1r), and produces yellow coats by inducing pheomelanin synthesis in hair follicular melanocytes. However, it is not known whether the Mc1re mutation affects the proliferation and differentiation of melanocytes. In this study, the proliferation and differentiation of recessive yellow epidermal melanocytes cultured in dibutyryl cyclic AMP-supplemented serum-free medium were investigated in detail. The melanocytes produced mainly eumelanin in this culture system. The proliferation of recessive yellow melanocytes was decreased compared with that of wild-type at the Mc1re-locus, black melanocytes. The differentiation of melanocytes was also delayed and inhibited in recessive yellow mice. Tyrosinase (Tyr) activity and Tyr-related protein 1 (Tyrp1) and Tyrp2 (dopachrome tautomerase, Dct) expressions were decreased and, in addition, the maturation of stage IV melanosomes was inhibited. Excess L-tyrosine added to the culture media rescued the reduced activity of proliferation of melanocytes. L-tyrosine also stimulated Tyr activity and Tyrp1 and Tyrp2 expressions as well as the maturation of stage IV melanosomes and pigmentation. These results suggest that the Mc1re mutation affects the proliferation and differentiation of melanocytes and L-tyrosine rescues the reduced proliferative and differentiative activities by stimulating Tyr activity and Tyrp1 and Tyrp2 expressions as well as melanosome maturation.14th Meeting of the European Society for Pigment Cell Researc