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

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

The Dowling-Meara variant of epidermolysis bullosa simplex (EBS-DM) is a severe blistering disease inherited in an autosomal-dominant fashion. Here we report the generation of a mouse model that allows focal activation of a mutant keratin 14 allele in epidermal stem cells upon topical administration of an inducer, resulting in EBS phenotypes in treated areas. Using laser capture microdissection, we show that induced blisters healed by migration of surrounding nonphenotypic stem cells into the wound bed. This observation provides an explanation for the lack of mosaic forms of EBS-DM. In addition, we show that decreased mutant keratin 14 expression resulted in normal morphology and functions of the skin. Our results have important implications for gene therapy of EBS and other dominantly inherited diseases.

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

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