An inducible mouse model for epidermolysis bullosa simplex: Implications for gene therapy

Tongyu Cao, Mary Ann Longley, Xiao Jing Wang, Dennis R. Roop

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)651-656
Number of pages6
JournalJournal of Cell Biology
Volume153
Issue number3
DOIs
StatePublished - Apr 30 2001
Externally publishedYes

Keywords

  • Epidermal stem cells
  • Epidermolysis bullosa simplex
  • Gene targeting
  • Gene therapy
  • Keratins

ASJC Scopus subject areas

  • Cell Biology

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