PMID: 8962131Dec 10, 1996Paper

A transgenic mouse model with an inducible skin blistering disease phenotype

Proceedings of the National Academy of Sciences of the United States of America
K Takahashi, P A Coulombe

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 so...Continue Reading

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Citations

Oct 8, 1999·Journal of Dermatological Science·K TakahashiY Miyachi
Mar 4, 1998·Current Opinion in Cell Biology·M K Houseweart, D W Cleveland
May 20, 2000·Biotechnology & Genetic Engineering Reviews·S BevanI A Mckay
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Dec 7, 2013·Veterinary Research·Gisela Soboll HusseyJosh Slater
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·J BrocardD Metzger
Oct 28, 2005·The Journal of Investigative Dermatology. Symposium Proceedings·Jiang Chen, Dennis R Roop
May 2, 2002·The Journal of Investigative Dermatology·Stacy MazzalupoPierre A Coulombe
Dec 16, 2006·The Journal of Investigative Dermatology·Li-Hong Gu, Pierre A Coulombe
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