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Focal activation of a mutant allele defines the role of stem cells in mosaic skin disorders.

ABSTRACT: 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 controlled 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.

SUBMITTER: Arin MJ

PROVIDER: S-EPMC2195990 | biostudies-literature | 2001 Feb

REPOSITORIES: biostudies-literature

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Focal activation of a mutant allele defines the role of stem cells in mosaic skin disorders.

Arin M J MJ Longley M A MA Wang X J XJ Roop D R DR

The Journal of cell biology 20010201 3

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 spat ...[more]

PMID: 11157989

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