Integrin mutations in blistering skin diseases and related genetically engineered mouse models.

As major receptors for cellular adhesion, integrins in the epidermis are critical to maintain skin integrity. Integrins α6β4 and α3β1 are among the most highly and widely expressed integrins in the skin. Perhaps not surprisingly, mutation in subunits associated with these integrins cause variations of a blistering skin disease called junctional epidermolysis bullosa (JEB), which is characterized by blisters that form between the epidermis and dermis of the skin.

Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis.

To date, studies of the role for epidermal integrin α3β1 in cutaneous wound re-epithelialization have produced conflicting results: wound studies in skin from global α3-null neonatal mice have implicated the integrin in promoting timely wound re-epithelialization, whereas studies in adult mice with constitutive, epidermal-specific α3β1 deletion have not. The objective of this study was to utilize a model of inducible α3β1 deletion in the epidermis to clarify the role of α3β1 in the healing of adult wounds. We utilized the recently developed transgenic K14::α3 mice (ie, inducible α3 epidermal knockout), permitting us to delete floxed alleles (α3) from epidermis just prior to wounding with topical treatment of 4-hydroxytamoxifen.