An Inducible Mouse Model for Epidermolysis Bullosa Simplex: Implications for Gene Therapy

doi:10.1083/jcb.152.3.651

Published online 5 February 2001. doi:10.1083/jcb.152.3.651

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© The Rockefeller University Press, 0021-9525/2001//651 $5.00
The Journal of Cell Biology, Volume 152, Number 3, , 2001 651-656

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An Inducible Mouse Model for Epidermolysis Bullosa Simplex

: Implications for Gene Therapy

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

roopd{at}bcm.tmc.edu

The Dowling-Meara variant of epidermolysis bullosa simplex (EBS-DM)is a severe blistering disease inherited in an autosomal-dominantfashion. Here we report the generation of a mouse model thatallows focal activation of a mutant keratin 14 allele in epidermalstem cells upon topical administration of an inducer, resultingin EBS phenotypes in treated areas. Using laser capture microdissection,we show that induced blisters healed by migration of surroundingnonphenotypic stem cells into the wound bed. This observationprovides an explanation for the lack of mosaic forms of EBS-DM.In addition, we show that decreased mutant keratin 14 expressionresulted in normal morphology and functions of the skin. Ourresults have important implications for gene therapy of EBSand other dominantly inherited diseases.

Key Words: epidermolysis bullosa simplex • gene therapy • gene targeting • epidermal stem cells • keratins

Abbreviations used in this paper: EBS, epidermolysis bullosasimplex; EBS-DM, Dowling-Meara variant of EBS; ES, embryonicstem; EHK, epidermolytic hyperkeratosis; IF, intermediate filament;neo, neomycin.

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