Inducible mouse models for inherited skin diseases: implications for skin gene therapy

Cells, Tissues, Organs
Meral J Arin, Dennis R Roop

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 develop...Continue Reading

Citations

Jul 10, 2010·Current Opinion in Pediatrics·Jo-David Fine
Aug 24, 2010·Ultramicroscopy·Valentin LulevichGang-yu Liu
Feb 13, 2008·The Journal of Investigative Dermatology·Ulrich R Hengge
Jun 16, 2011·The Journal of Investigative Dermatology·Paul E Bowden
Mar 11, 2006·The Journal of Investigative Dermatology·Kelly A McGowanGregory S Barsh
Mar 24, 2009·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Peter Itin, Bettina Burger
Jun 12, 2010·Annals of the New York Academy of Sciences·Jo-David Fine

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.