Development of a novel pink-eyed dilution mouse model showing progressive darkening of the eyes and coat hair with aging

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Author(s)

    • ISHIKAWA Akira ISHIKAWA Akira
    • Laboratory of Animal Genetics, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
    • SUGIYAMA Makoto SUGIYAMA Makoto
    • Laboratory of Animal Morphology and Function, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan|Present address: Laboratory of Veterinary Anatomy, School of Veterinary Medicine, Kitasato University, Higashi, Towada, Aomori 034-8628, Japan
    • HONDO Eiichi [他] HONDO Eiichi
    • Laboratory of Animal Morphology and Function, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
    • KINOSHITA Keiji
    • Laboratory of Animal Genetics, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
    • YAMAGISHI Yuki
    • Laboratory of Animal Genetics, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan

Abstract

<i>Oca2<sup>p-cas</sup></i> (oculocutaneous albinism II; pink-eyed dilution castaneus) is a coat color mutant gene on mouse chromosome 7 that arose spontaneously in wild <i>Mus musculus castaneus</i> mice. Mice homozygous for <i>Oca2<sup>p-cas</sup></i> usually exhibit pink eyes and gray coat hair on the non-agouti genetic background, and this ordinary phenotype remains unchanged throughout life. During breeding of a mixed strain carrying this gene on the C57BL/6J background, we discovered a novel spontaneous mutation that causes darkening of the eyes and coat hair with aging. In this study, we developed a novel mouse model showing this unique phenotype. Gross observations revealed that the pink eyes and gray coat hair of the novel mutant young mice became progressively darker in color by approximately 3 months after birth. Light and transmission-electron microscopic observations revealed a marked increase in melanin pigmentation of coat hair shafts and choroid of the eye in the novel mice compared to that in the ordinary mice. Sequence analysis of <i>Oca2<sup>p-cas</sup></i> revealed a 4.1-kb deletion involving exons 15 and 16 of its wild-type gene. However, there was no sequence difference between the two types of mutant mice. Mating experiments suggested that the novel mutant phenotype was not inherited in a simple fashion, due to incomplete penetrance. The novel spontaneous mutant mouse is the first example of progressive hair darkening animals and is an essential animal model for understanding of the regulation mechanisms of melanin biosynthesis with aging.

Journal

  • Experimental Animals

    Experimental Animals 64(2), 207-220, 2015

    Japanese Association for Laboratory Animal Science

Codes

  • NII Article ID (NAID)
    130005069866
  • NII NACSIS-CAT ID (NCID)
    AA11032321
  • Text Lang
    ENG
  • ISSN
    1341-1357
  • NDL Article ID
    026335884
  • NDL Call No.
    Z54-H752
  • Data Source
    NDL  J-STAGE 
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