A transgenic mouse model with an inducible skin blistering disease phenotype

Kenzo Takahashi, Pierre A. Coulombe

Research output: Contribution to journalArticle

Abstract

One of the current limitations of gene transfer protocols involving mammalian genomes is the lack of spatial and temporal control over the desired gene manipulation. Starting from a human keratin gene showing a complex regulation as a template, we identified regulatory sequences that confer inducible gene expression in a subpopulation of keratinocytes in stratified epithelia of adult transgenic mice. We used this cassette to produce transgenic mice with an inducible skin blistering phenotype mimicking a form of epidermolytic hyperkeratosis, a keratin gene disorder. Upon induction by topical application of a phorbol ester, the mutant keratin transgene product accumulates in the differentiating layers of epidermis, leading to keratinocyte lysis after application of mechanical trauma. This mouse model will allow for a better understanding of the complex relationship between keratin mutation, keratinocyte cytoarchitecture, and hypersensitivity to trauma. The development of an inducible expression vector showing an exquisite cellular specificity has important implications for manipulating genes in a spatially and temporally controlled fashion in transgenic mice, and for the design of gene therapy strategies using skin as a tissue source for the controlled delivery of foreign substances.

Original languageEnglish (US)
Pages (from-to)14776-14781
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number25
StatePublished - Dec 10 1996

Fingerprint

Skin Diseases
Transgenic Mice
Keratins
Phenotype
Keratinocytes
Genes
Epidermolytic Hyperkeratosis
Skin
Wounds and Injuries
Phorbol Esters
Transgenes
Epidermis
Genetic Therapy
Hypersensitivity
Epithelium
Genome
Gene Expression
Mutation

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

A transgenic mouse model with an inducible skin blistering disease phenotype. / Takahashi, Kenzo; Coulombe, Pierre A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 25, 10.12.1996, p. 14776-14781.

Research output: Contribution to journalArticle

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