A novel deletion mutation of mouse ruby-eye 2 named ru2 d/ Hps5 ru2-d inhibits melanocyte differentiation and its impaired differentiation is rescued by L-tyrosine

Tomohisa Hirobe, Chihiro Yoshihara, Sakae Takeuchi, Kazumasa Wakamatsu, Shosuke Ito, Hiroyuki Abe, Yoko Kawa, Yoshinao Soma

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In our laboratory, a single autosomal recessive mutation in a phenotype similar to ruby-eye (ru/Hps6 ru) or ruby-eye 2 (ru2/Hps5 ru2) spontaneously occurred in siblings of C57BL/10JHir (+/+, black) mice in 2006. RT-PCR analysis revealed that this novel mutation, named ru2 d/Hps5 ru2-d, exhibited frameshift by 997G deletion in the Hps5 gene. To clarify the mechanism of the hypopigmentation, the characteristics of proliferation and differentiation of ru2 d/ru2 d epidermal melanoblasts and melanocytes cultured in a serum-free medium were investigated. The proliferation of ru2 d/ru2 d melanoblasts and melanocytes did not differ from that of +/+ melanoblasts and melanocytes. However, the differentiation of ru2 d/ru2 d melanocytes was greatly inhibited. Tyrosinase (TYR) activity, expression of TYR, TYR-related protein 1 (TRP1) and TRP2 (dopachrome tautomerase, DCT), eumelanin synthesis, and the number of stage IV melanosomes markedly decreased in ru2 d/ru2 d melanocytes. However, excess L-tyrosine (Tyr) added to culture media from initiation of the primary culture rescued the reduced differentiation through increase in TYR activity, expression of TYR, TRP1, TRP2 and Kit, eumelanin synthesis, and stage IV melanosomes. L-Tyr injected into ru2 d/ru2 d mice also stimulated melanocyte differentiation. These results suggest that the ru2 d allele inhibits melanocyte differentiation, and that its impaired differentiation is rescued by excess Tyr.

Original languageEnglish
Pages (from-to)790-801
Number of pages12
JournalZoological Science
Issue number11
Publication statusPublished - Nov 2011



  • Hermansky-Pudlak syndrome
  • melanocyte
  • melanosome
  • ruby-eye
  • tyrosinase

ASJC Scopus subject areas

  • Animal Science and Zoology

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