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

doi:10.1083/jcb.152.3.645

Published online 5 February 2001. doi:10.1083/jcb.152.3.645

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© The Rockefeller University Press, 0021-9525/2001/2/645/ $5.00
The Journal of Cell Biology, Volume 152, Number 3, February 5, 2001 645-650

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

Meral J. Arin^a, Mary Ann Longley^a, Xiao-Jing Wang^a,b, and Dennis R. Roop^a,b
^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

Correspondence to: Dennis R. Roop, Baylor College of Medicine, Department of Molecular and Cellular Biology, One Baylor Plaza, Houston, TX 77030. Tel:(713) 798-4966 Fax:(713) 798-3800 E-mail:roopd{at}bcm.tmc.edu.

Stem cells are crucial for the formation and maintenance oftissues and organs. The role of stem cells in the pathogenesisof mosaic skin disorders remains unclear. To study the molecularand cellular basis of mosaicism, we established a mouse modelfor the autosomal-dominant skin blistering disorder, epidermolytichyperkeratosis (MIM 113800), which is caused by mutations ineither keratin K1 or K10. This genetic model allows activationof a somatic K10 mutation in epidermal stem cells in a spatiallyand temporally controlled manner using an inducible Cre recombinase.Our results indicate that lack of selective pressure againstcertain mutations in epidermal stem cells leads to mosaic phenotypes.This finding has important implications for the developmentof new strategies for somatic gene therapy of dominant genodermatoses.

Key Words: epidermolytic hyperkeratosis, keratins, Cre recombinase, mosaicskin disease, gene therapy

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