title: A new mutation of mouse ruby-eye 2, ru2(d)/Hps5(ru2-d) inhibits eumelanin synthesis but stimulates pheomelanin synthesis in melanocytes.
abstract: We previously demonstrated that a novel mutation, characterized by light-colored coats and ruby eyes, which occurred spontaneously in mice in our laboratory, exhibited deletion in the Hps5 gene (ru2(d)/Hps5(ru2-d)). To clarify the mechanism of this hypopigmentation, the characteristics of the neonatal development of ru2(d)/ru2(d)  melanocytes were investigated in detail with special reference to those of +/+ melanocytes. In ru2(d)/ru2(d)  mice, there were fewer epidermal melanocytes than in +/+ mice, whereas there was no difference in numbers of epidermal melanoblasts in +/+ and ru2(d)/ru2(d)mice, both in dorsal and ventral skin. Epidermal melanocytes with increased dopa-melanin deposition and dendritogenesis were greatly increased by injecting L-Tyr subcutaneously into newborn ru2(d)/ru2(d) mice. The eumelanin content in the epidermis and dermis in postnatal ru2(d)/ru2(d)  mice was much lower than in +/+ mice, whereas similar pheomelanin content was observed 5.5 or 7.5 days after birth both in dorsal and ventral skins. Moreover, the eumelanin content in the dorsal and ventral hairs in 5-week-old ru2(d)/ru2(d)  mice was much lower than in +/+ mice, whereas pheomelanin content was two to four times greater than in +/+ mice. These results suggest that the ru2(d)  allele suppresses the differentiation of melanocytes through the inhibition of eumelanin synthesis, but stimulates pheomelanin synthesis in melanocytes.
authors.affiliation: Radiation Risk Reduction Research Program, National Institute of Radiological Sciences, Chiba 263-8555, Japan. thirobe@nirs.go.jp
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hirobe
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000078404:Epidermal Cells; D006197:Hair; D008543:Melanins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008544:Melanocytes / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008543:Melanins; D011506:Proteins; C018362:pheomelanin; C570393:ruby-eye 2 protein, mouse; C041877:eumelanin