三毛猫の毛色を決める遺伝子をついに発見〜60 年間の謎だった三毛猫の毛色の仕組みを解明〜

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2025-05-16 九州大学

九州大学の佐々木裕之特別主幹教授らの研究チームは、三毛猫やサビ猫の毛色に関与する「オレンジ遺伝子」が、X染色体上のARHGAP36遺伝子であることを世界で初めて特定した。福岡市内の猫18匹のDNA解析で、この遺伝子に約5,000塩基の欠失があることを発見し、50匹以上の追加調査と海外データでも完全一致が確認された。欠失によりARHGAP36の発現が上昇し、メラニン合成が黒からオレンジへと切り替わることが示唆された。研究成果は『Current Biology』に掲載。

<関連情報>

X-連鎖性ARHGAP36遺伝子座の欠失は三毛猫や三毛猫のオレンジ色に関連する A deletion at the X-linked ARHGAP36 gene locus is associated with the orange coloration of tortoiseshell and calico cats

Hidehiro Toh ∙ Wan Kin Au Yeung,, ∙ Motoko Unoki ∙ … ∙ Yasukazu Nakamura ∙ Miho Matsuda ∙ Hiroyuki Sasaki
Current Biology  Published:May 15, 2025
DOI:https://doi.org/10.1016/j.cub.2025.03.075

Graphical abstract

三毛猫の毛色を決める遺伝子をついに発見〜60 年間の謎だった三毛猫の毛色の仕組みを解明〜

Highlights

  • X-linked ARHGAP36 is identified as the gene responsible for the orange coat of cats
  • A deletion at this locus alters ARHGAP36 expression, leading to pigment-type switch
  • Evidence suggests that ARHGAP36 is subject to random X chromosome inactivation
  • The deletion seems widespread in cats, suggesting a single origin of this phenotype

Summary

The X-linked orange (O) locus in domestic cats controls an unknown molecular mechanism that causes the suppression of black-brownish pigmentation in favor of orange coloration. The alternating black-brownish and orange patches seen in tortoiseshell and calico cats are considered classic examples of the phenotypic expression of random X chromosome inactivation (XCI) occurring in female mammals. However, the O gene in the cat genome has not been identified, and the genetic variation responsible for the orange coloration remains unknown. We report here that a 5.1-kilobase (kb) deletion within an intron of the X-linked ARHGAP36 gene, encoding a Rho GTPase-activating protein, is closely and exclusively associated with orange coloration. The deleted region contains a highly conserved putative regulatory element, whose removal is presumed to alter ARHGAP36 expression. Notably, ARHGAP36 expression in cat skin tissues is linked to the suppression of many melanogenesis genes, potentially shifting pigment synthesis from eumelanin to pheomelanin. Furthermore, we find evidence that the gene undergoes XCI in female human and mouse cells and XCI-dependent CpG island methylation consistent with random XCI in female domestic cats. The 5.1-kb deletion seems widespread in domestic cats with orange coat coloration, suggesting a single origin of this coat color phenotype.

生物工学一般
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