title: Functional conservation of Gsdma cluster genes specifically duplicated in the mouse genome.
abstract: 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.
authors: Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8450, Japan.
authors: Shigekazu
authors: S
authors: Tanaka
authors: Youichi
authors: Y
authors: Mizushina
authors: Yoriko
authors: Y
authors: Kato
authors: Masaru
authors: M
authors: Tamura
authors: Toshihiko
authors: T
authors: Shiroishi
mesh_terms: D000505:Alopecia / Q000235:genetics; D000818:Animals; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D020440:Gene Duplication; D016678:Genome; D006965:Hyperplasia / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D000094524:Gasdermins
chemical_list: D009363:Neoplasm Proteins; D011506:Proteins; C413482:Gsdma protein, mouse; D000094524:Gasdermins; C499121:Gsdma3 protein, mouse
keywords: Gasdermin A; alopecia; duplication; knockout; transgenic
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