Tanaka Shigekazu, Tamura Masaru, Aoki Aya, Fujii Tomoaki, Komiyama Hiromitsu, Sagai Tomoko, Shiroishi Toshihiko
Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
Biochem Biophys Res Commun. 2007 Aug 10;359(4):902-7. doi: 10.1016/j.bbrc.2007.05.209. Epub 2007 Jun 8.
Recombination-induced mutation 3 (Rim3) is a spontaneous mouse mutation that exhibits dominant phenotype of hyperkeratosis and hair loss. Fine linkage analysis of Rim3 and sequencing revealed a novel single point mutation, G1124A leading to Ala348Thr, in Gsdma3 in chromosome 11. Transgenesis with BAC DNA harboring the Rim3-type Gsdma3 recaptured the Rim3 phenotype, providing direct evidence that Gsdma3 is the causative gene of Rim3. We examined the spatial expression of Gsdma3 and characterized the Rim3 phenotype in detail. Gsdma3 is expressed in differentiated epidermal cells in the skin, but not in the proliferating epidermal cells. Histological analysis of Rim3 mutant showed hyperplasia of the epidermal cells in the upper hair follicles and abnormal anagen phase at the first hair cycle. Furthermore, immunohistochemical analysis revealed hyperproliferation and misdifferentiation of the upper follicular epidermis in Rim3 mutant. These results suggest that Gsdma3 is involved in the proliferation and differentiation of epidermal stem cells.
重组诱导突变3（Rim3）是一种自发的小鼠突变，表现出角质化过度和脱发的显性表型。对Rim3进行精细连锁分析和测序后，在11号染色体的Gsdma3中发现了一个新的单点突变G1124A，该突变导致Ala348Thr。用携带Rim3型Gsdma3的BAC DNA进行转基因实验重现了Rim3表型，这直接证明Gsdma3是Rim3的致病基因。我们检测了Gsdma3的空间表达，并详细描述了Rim3的表型。Gsdma3在皮肤中分化的表皮细胞中表达，但在增殖的表皮细胞中不表达。对Rim3突变体的组织学分析显示，上毛囊中的表皮细胞增生，且在第一个毛发周期的生长期异常。此外，免疫组织化学分析显示，Rim3突变体中上毛囊表皮细胞过度增殖且分化异常。这些结果表明，Gsdma3参与表皮干细胞的增殖和分化。
