A new Gsdma3 mutation affecting anagen phase of first hair cycle
A new Gsdma3 mutation affecting anagen phase of first hair cycle
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DOI：
10.1016/j.bbrc.2007.05.209
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发表时间：
2007-08-10
影响因子：
3.1
通讯作者：
Shiroishi, Toshihiko
中科院分区：
文献类型：
--
作者：
Tanaka, Shigekazu;Tamura, Masaru;Shiroishi, Toshihiko
重组诱导突变3(Rim3)是一种自发突变的小鼠，主要表现为角化过度和脱发。Rim3的精细连锁分析和测序显示，在11号染色体的Gsdma3中发现了一个新的单点突变G1124A，导致Ala348Thr。携带Rim3型Gsdma3的BAC DNA转基因获得了Rim3表型，为Gsdma3是Rim3的致病基因提供了直接证据。我们检测了Gsdma3的空间表达，并详细描述了Rim3的表型。Gsdma3在皮肤分化的表皮细胞中表达，但在增殖的表皮细胞中不表达。Rim3突变体的组织学分析显示，在第一个毛发周期，上毛囊中的表皮细胞增生，生长期异常。免疫组织化学分析显示，Rim3突变体的上毛囊表皮过度增殖和分化不良。这些结果提示Gsdma3参与了表皮干细胞的增殖和分化。(C)2007 Elsevier Inc.保留所有权利。
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. (c) 2007 Elsevier Inc. All rights reserved.