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| Inducible mouse models for inherited skin diseases: Implications for skin gene therapy |
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| Author(s): Arin MJ, Roop DR |
| Source: CELLS TISSUES ORGANS Volume: 177 Issue: 3 Pages: 160-168 Published: 2004 |
| Times Cited: 9 References: 23 |
| Abstract: Stem cells are crucial for the formation and maintenance of tissues and organs. To understand the role of stem cells in the pathogenesis of mosaic skin disorders, we generated inducible mouse models for two autosomal dominant keratin disorders, epidermolytic hyperkeratosis (EHK) and epidermolysis bullosa simplex (EBS), that enable activation of the respective mutation in epidermal stem cells in a spatially and temporally controlled manner using a ligand-inducible Cre recombinase. Whereas mosaic forms have been reported for EHK, which is caused by mutations in the suprabasal keratins K1 or K10, this has never been reported for EBS, which is due to mutations in the basal keratins K5 or K14. When we induced the phenotype in these models by topical application of the inducer, we found phenotypic areas in the EHK model that persisted for the life of the mouse. On the contrary, the induced blisters in the EBS model healed within a few weeks by migration of surrounding non-phenotypic stem cells into the wound bed. Our results indicate that lack of selective pressure against certain mutations in epidermal stem cells could explain why mosaic forms exist for EHK, but not for EBS. These findings have important implications for the development of new strategies for somatic gene therapy of dominant genodermatoses, and we are currently using these inducible mouse models to test gene therapy approaches. Copyright (C) 2004 S. Karger AG, Basel. |
| Document Type: Proceedings Paper |
| Language: English |
| Reprint Address: Roop, DR (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA |
Addresses:
1. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
2. Univ Cologne, Dept Dermatol, D-5000 Cologne, Germany
3. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA |
| Publisher: KARGER, ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND |
| Subject Category: Anatomy & Morphology; Cell Biology; Developmental Biology |
| IDS Number: 852LM |
| ISSN: 1422-6405 |
| DOI: 10.1159/000079990 |
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