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© The Rockefeller University Press, 0021-9525/2001//645 $5.00
The Journal of Cell Biology, Volume 152, Number 3, , 2001 645-650

Focal Activation of a Mutant Allele Defines the Role of Stem Cells in Mosaic Skin Disorders

^a Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030
^b Department of Dermatology, Baylor College of Medicine, Houston, Texas 77030
Baylor College of Medicine, Department of Molecular and Cellular Biology, One Baylor Plaza, Houston, TX 77030.(713) 798-3800(713) 798-4966

roopd{at}bcm.tmc.edu

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.

Key Words: epidermolytic hyperkeratosis • keratins • Cre recombinase • mosaic skin disease • gene therapy

© 2001 The Rockefeller University Press

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