Functional conservation of Gsdma cluster genes specifically duplicated in the mouse genome.
Functional conservation of Gsdma cluster genes specifically duplicated in the mouse genome.
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DOI：
10.1534/g3.113.007393
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发表时间：
2013-10-03
期刊：
影响因子：
--
通讯作者：
Shiroishi T
中科院分区：
文献类型：
--
作者：
Tanaka S;Mizushina Y;Kato Y;Tamura M;Shiroishi T
小鼠Gasdermin A3（Gsdma 3）是表现出脱发的显性皮肤突变的致病基因。小鼠有另外两个Gsdma 3相关基因，Gsdma和Gsdma 2，而人类和大鼠只有一个相关基因。到目前为止，还没有关于人类GSDMA和大鼠Gsdma以及小鼠Gsdma和Gsdma 2的皮肤突变的报道。因此，可能只有Gsdma 3具有功能获得型突变，从而导致显性皮肤表型。为了阐明小鼠中Gsdma相关基因之间的功能差异，并推断人类和大鼠直系同源物的功能，我们通过产生Gsdma敲除小鼠和过表达野生型Gsdma或Gsdma携带点突变（丙氨酸339苏氨酸）的转基因小鼠来检查小鼠Gsdma的体内功能。Gsdma基因敲除小鼠没有表现出明显的表型，表明Gsdma对表皮细胞的分化和毛发周期的维持不是必需的，并且Gsdma在毛囊的内根鞘和基底上细胞层中特异性表达，而Gsdma 3仅在基底上细胞层中表达。相比之下，这两种类型的转基因小鼠表现出表皮增生类似Gsdma 3突变，虽然表型依赖于遗传背景。这些结果表明，小鼠Gsdma和Gsdma 3基因具有共同的功能，以调节上皮细胞的维持和/或稳态，并表明，人GSDMA和大鼠Gsdma，这是小鼠Gsdma的直系同源物，功能也是保守的。
Mouse Gasdermin A3 (Gsdma3) is the causative gene for dominant skin mutations exhibiting alopecia. Mouse has two other Gsdma3-related genes, Gsdma and Gsdma2, whereas human and rat have only one related gene. To date, no skin mutation has been reported for human GSDMA and rat Gsdma as well as mouse Gsdma and Gsdma2. Therefore, it is possible that only Gsdma3 has gain-of-function type mutations to cause dominant skin phenotype. To elucidate functional divergence among the Gsdma-related genes in mice, and to infer the function of the human and rat orthologs, we examined in vivo function of mouse Gsdma by generating Gsdma knockout mice and transgenic mice that overexpress wild-type Gsdma or Gsdma harboring a point mutation (Alanine339Threonine). The Gsdma knockout mice shows no visible phenotype, indicating that Gsdma is not essential for differentiation of epidermal cells and maintenance of the hair cycle, and that Gsdma is expressed specifically both in the inner root sheath of hair follicles and in suprabasal cell layers, whereas Gsdma3 is expressed only in suprabasal layers. By contrast, both types of the transgenic mice exhibited epidermal hyperplasia resembling the Gsdma3 mutations, although the phenotype depended on the genetic background. These results indicate that the mouse Gsdma and Gsdma3 genes share common function to regulate epithelial maintenance and/or homeostasis, and suggest that the function of human GSDMA and rat Gsdma, which are orthologs of mouse Gsdma, is conserved as well.
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小鼠基因组中最近的分段和基因重复。
影响因子：
12.3
作者：
Cheung, Joseph;Wilson, Michael D;Zhang, Junjun;Khaja, Razi;MacDonald, Jeffrey R;Heng, Henry H Q;Koop, Ben F;Scherer, Stephen W
通讯作者：
Scherer, Stephen W
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影响因子：
2.3
作者：
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6.5
作者：
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通讯作者：
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影响因子：
6.5
作者：
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通讯作者：
Porter, RM
影响因子：
2.5
作者：
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通讯作者：
Shiroishi, T