Focal activation of a mutant allele defines the role of stem cells in mosaic skin disorders
Focal activation of a mutant allele defines the role of stem cells in mosaic skin disorders
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DOI：
10.1083/jcb.152.3.645
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发表时间：
2001-02-05
影响因子：
7.8
通讯作者：
Roop, DR
中科院分区：
文献类型：
--
作者：
Arin, MJ;Longley, MA;Roop, DR
干细胞对组织和器官的形成和维持至关重要。干细胞在马赛克皮肤病发病机制中的作用尚不清楚。为了研究嵌合体的分子和细胞基础，我们建立了一种常染色体显性显性皮肤起泡性疾病--表皮松解性角化过度症(MIM 113800)的小鼠模型，该疾病是由角蛋白K1或K10的突变引起的。这一遗传模型允许利用可诱导的Cre重组酶以空间和时间控制的方式激活表皮干细胞中的体细胞K10突变。我们的结果表明，缺乏对表皮干细胞某些突变的选择压力会导致镶嵌表型。这一发现对于开发显性遗传性皮肤病的体细胞基因治疗的新策略具有重要意义。
Stem cells are crucial for the formation and maintenance of tissues and organs. The role of stem cells in the pathogenesis of mosaic skin disorders remains unclear. To study the molecular and cellular basis of mosaicism, we established a mouse model for the autosomal-dominant skin blistering disorder, epidermolytic hyperkeratosis (MIM 113800), which is caused by mutations in either keratin K1 or K10. This genetic model allows activation of a somatic K10 mutation in epidermal stem cells in a spatially and temporally con-trolled manner using an inducible Cre recombinase, Our results indicate that lack of selective pressure against certain mutations in epidermal stem cells leads to mosaic phenotypes. This finding has important implications for the development of new strategies for somatic gene therapy of dominant genodermatoses.