Okada Taro, Ishii Yoshiyuki, Masujin Kentaro, Yasoshima Akira, Matsuda Junichiro, Ogura Atsuo, Nakayama Hiroyuki, Kunieda Tetsuo, Doi Kunio
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
Am J Pathol. 2006 Apr;168(4):1119-33. doi: 10.2353/ajpath.2006.050507.
Mutation in the serum/glucocorticoid regulated kinase 3 (Sgk3, also known as Sgkl or Cisk) gene causes both defective hair follicle development and altered hair cycle in mice. We examined Sgk3-mutant YPC mice (YPC-Sgk3(ypc)/Sgk3(ypc)) and found expression of SGK3 protein with altered function. In the hair follicles of YPC mice, the aberrant differentiation and poor proliferation of hair matrix keratinocytes during the period of postnatal hair follicle development resulted in a complete lack of hair medulla and weak hair. Surprisingly, the length of postnatal hair follicle development and anagen term was shown to be dramatically shortened. Also, phosphorylation of GSK3beta at Ser9 and the nuclear accumulation of beta-catenin were reduced in the developing YPC hair follicle, suggesting that phosphorylation of GSK3beta and WNT-beta-catenin pathway takes part in the SGK3-dependent regulation of hair follicle development. Moreover, the above-mentioned features, especially the hair-cycling pattern, differ from those in other Sgk3-null mutant strains, suggesting that the various patterns of dysfunction in the SGK3 protein may result in phenotypic variation. Our results indicate that SGK3 is a very important and characteristic molecule that plays a critical role in both hair follicle morphogenesis and hair cycling.
血清/糖皮质激素调节激酶3（Sgk3，也称为Sgkl或Cisk）基因的突变会导致小鼠毛囊发育缺陷和毛发周期改变。我们检测了Sgk3突变的YPC小鼠（YPC-Sgk3(ypc)/Sgk3(ypc)），发现了功能改变的SGK3蛋白表达。在YPC小鼠的毛囊中，出生后毛囊发育期间毛发基质角质形成细胞的异常分化和增殖不良导致完全缺乏毛髓质且毛发脆弱。令人惊讶的是，出生后毛囊发育的长度和生长期明显缩短。此外，在发育中的YPC毛囊中，GSK3β在Ser9位点的磷酸化以及β-连环蛋白的核积累减少，这表明GSK3β的磷酸化和WNT-β-连环蛋白信号通路参与了SGK3依赖的毛囊发育调节。而且，上述特征，尤其是毛发周期模式，与其他Sgk3基因敲除突变株不同，这表明SGK3蛋白功能障碍的各种模式可能导致表型变异。我们的结果表明，SGK3是一个非常重要且具有特征性的分子，在毛囊形态发生和毛发周期中都起着关键作用。
