Mechanism of regulation of melanin synthesis by coat color genes and ultraviolet radiation in mice and human

在黑色黑素细胞（Dct^+）中，几乎所有的黑素小体都是椭圆形的IV期黑素小体。然而，在板状（Dctslt）黑素细胞中，除了观察到椭圆形的III期黑素小体与腔内原纤维外，还观察到许多球形的III期黑素小体与球状的色素沉积。在板状黑素细胞中，球形黑素体在出生后逐渐减少，椭圆形黑素体逐渐增加。IV期黑素小体在石板黑素细胞中很少，出生后不增加。l -酪氨酸增加了椭圆型IV期黑素体，增加了真黑素和泛黑素的合成。这些结果表明，sly突变在III期阻断了黑素体的成熟并影响了黑素体的形态，而l -酪氨酸恢复了这些异常。在我们的培养系统中，隐性黄色（Mclre）黑色素细胞主要产生真黑色素。与野生型相比，隐性黄色黑素细胞在e位点黑色黑素细胞的增殖减少。在隐性黄小鼠中，黑素细胞的分化也被延迟和抑制。酪氨酸酶（TYR）活性和TYR相关蛋白1 （TRP1）、TRP2 （dopachrome tamautoerase， DCT）表达降低，IV期黑素小体成熟受到抑制。在培养基中添加过量的l -酪氨酸（Tyr）可以挽救黑色素细胞增殖活性降低的情况。L-Tyr还刺激了TYR活性、TRP1和TRP2的表达，以及IV期黑素体的成熟和色素沉着。这些结果表明，Mclre突变影响黑素细胞的增殖和分化，L-Tyr通过刺激TYR活性、TRP1和TRP2表达以及黑素小体成熟来挽救黑色素细胞增殖和分化活性的降低。

In black melanocytes (Dct^+), almost all melanosomes were elliptical stage IV melanosomes. However, in slaty (Dctslt) melanocytes, numerous spherical stage III melanosomes with globular depositions of pigment in addition to elliptical stage III melanosomes with intralumenal fibrils were observed. In slaty melanocytes, spherical melanosomes were gradually decreased after birth, whereas elliptical melanosomes were gradually increased. Stage IV melanosomes were very few in slaty melanocytes, and were not increased after birth. L-tyrosine increased the elliptical stage IV melanosomes, and eumelanin and pheomelanin synthesis. These results suggest that the slaty mutation blocks the melanosome maturation at stage III and affects the melanosome morphology and L-tyrosine restores these abnormalities.The recessive yellow (Mclre) melanocytes produced mainly eumelanin in our culture system. The proliferation of recessive yellow melanocytes was decreased compared with that of wild-type at the e-locus, black melanocytes. The differentiation of melanocytes was also delayed and inhibited in recessive yellow mice. Tyrosinase (TYR) activity and TYR-related protein 1 (TRP1) and TRP2 (dopachrome tautomerase, DCT) expressions were decreased and, in addition, the maturation of stage IV melanosomes was inhibited. Excess L-tyrosine (Tyr) added to the culture media rescued the reduced activity of proliferation of melanocytes. L-Tyr also stimulated TYR activity and TRP1 and TRP2 expressions as well as the maturation of stage IV melanosomes and pigmentation. These results suggest that the Mclre mutation affects the proliferation and differentiation of melanocytes and L-Tyr rescues the reduced proliferative and differentiative activities by stimulating TYR activity and TRP1 and TRP2 expressions as well as melanosome maturation.