Association of a mutation in TRPV3 with defective hair growth in rodents
Association of a mutation in TRPV3 with defective hair growth in rodents
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DOI：
10.1038/sj.jid.5700468
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发表时间：
2006-12-01
影响因子：
6.5
通讯作者：
Sakata, Tsuneaki
中科院分区：
文献类型：
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作者：
Asakawa, Makoto;Yoshioka, Takeshi;Sakata, Tsuneaki
DS-Nh 小鼠和 WBN/Kob-Ht 大鼠是自发无毛突变啮齿动物品系。这些动物在正常情况下会出现自发性皮炎。非毛发Nh和Ht表型以常染色体显性方式遗传，并且Nh突变具有高效的穿透能力。我们之前报道过，与皮炎和脱毛有关的基因并没有相互分离。在这里，我们进行了遗传分析，以确定导致这些无毛突变的基因。在 DS-Nh 小鼠和 WBN/Kob-Ht 大鼠中检测到一个基因中同一位置的氨基酸取代：Gly573 至 Ser（Nh 突变）或 Gly573 至 Cys（Ht 突变），位于瞬时受体电位 (TRP) 阳离子通道亚家族 V 成员 3 (TRPV3) 基因中。突变的 TRPV3 在 DS-Nh 小鼠的皮肤角质形成细胞中表达。组织病理学分析显示，与年龄匹配的亲本品系相比，两种啮齿动物皮肤病变中的肥大细胞均有所增加，这可能部分归因于无毛和皮炎。我们得出结论，TRPV3 是导致 Nh 和 Ht 突变的基因，TRPV3 的突变可能与肥大细胞数量增加相关。
DS-Nh mice and WBN/Kob-Ht rats are spontaneous hairless mutant rodent strains. These animals develop spontaneous dermatitis under normal conditions. The non-hair Nh and Ht phenotypes are inherited in an autosomal dominant fashion, and the Nh mutation possesses a high potency for penetration. We previously reported that genes involved in dermatitis and hairlessness did not segregate from each other. Here, we carried out genetic analysis to identify the genes responsible for these hairless mutations. An amino-acid substitution at the same position in one gene was detected in DS-Nh mice and WBN/Kob-Ht rats: Gly573 to Ser (Nh mutation) or Gly573 to Cys (Ht mutation), located in the transient receptor potential (TRP) cation channel subfamily V member 3 (TRPV3) gene. Mutated TRPV3 was expressed in skin keratinocytes of DS-Nh mice. Histopathological analyses revealed that mast cells in skin lesions were increased in both rodents compared to their age-matched parent strains, and that this may partially be due to hairlessness and dermatitis. We concluded that TRPV3 was the gene responsible for Nh and Ht mutations, and that mutation in TRPV3 possibly correlated with increased mast cell numbers.