Sasaki Takashi, Shiohama Aiko, Amagai Masayuki
Department of Dermatology, Keio University, School of Medicine.
Nihon Rinsho Meneki Gakkai Kaishi. 2014;37(3):160-5. doi: 10.2177/jsci.37.160.
Flaky tail mice possess two distinct autosomal recessive mutations, hair abnormality (matted: ma) and stratum corneum layer abnormality (flaky tail: ft), and develop dermatitis spontaneously with high serum IgE even under specific pathogen free condition. We demonstrated that flaky tail mice possess loss of function mutation in Filaggrin (Flg) which is one of the major component of stratum corneum, and showed skin barrier abnormality, although our genetically engineered Flg null mice did not develop dermatitis spontaneously. As a result of segregation of ft and ma mutations, we identified that ma mutation is responsible for the dermatitis phenotype in flaky tail mice, and Tmem79 nonsense mutation (Tmem79(ma)) is corresponding to the ma mutation. Tmem79 is expressed in outermost cell of stratum granulosum layer, and ma mice showed abnormal lamellar granule secretory system and abnormal formation of stratum corneum. Thus, Tmem79(ma/ma) mice provides a useful mouse model for spontaneous dermatitis caused by skin barrier gene deficiency. Further analysis for Tmem79(ma/ma) mice would elucidate important mechanisms for development of atopic dermatitis.
片状尾小鼠存在两种不同的常染色体隐性突变，即毛发异常（缠结：ma）和角质层异常（片状尾：ft），即使在无特定病原体条件下也会自发发生皮炎且血清IgE水平较高。我们证明，片状尾小鼠的丝聚合蛋白（Flg）存在功能缺失突变，丝聚合蛋白是角质层的主要成分之一，片状尾小鼠表现出皮肤屏障异常，尽管我们的基因工程Flg基因敲除小鼠不会自发发生皮炎。由于ft和ma突变的分离，我们确定ma突变是片状尾小鼠皮炎表型的原因，跨膜蛋白79无义突变（Tmem79(ma)）与ma突变相对应。Tmem79在颗粒层最外层细胞中表达，ma小鼠表现出板层颗粒分泌系统异常和角质层形成异常。因此，Tmem79(ma/ma)小鼠为皮肤屏障基因缺陷引起的自发性皮炎提供了一种有用的小鼠模型。对Tmem79(ma/ma)小鼠的进一步分析将阐明特应性皮炎发生发展的重要机制。
