Pathological meprin a activity associated with degradation of dermokine drives a psoriasis-like skin phenotype in a novel genetic mouse model

Keratinocyte proliferation and differentiation is regulated via proteolytic networks. Dysregulation of proteases within these systems can cause hyperproliferative and inflammatory skin disorders. In healthy skin the metalloprotease meprin α is localized in the stratum basale, yet in wound healing tissue and psoriatic lesions meprin α is synthesized at higher levels and translocalized to upper epidermal layers. We developed a transgenic mouse model for inducible expression of pathological meprin α levels (K5Mα) to investigate its epidermal degradome and, thereby, identify molecular links to keratinocyte proliferation and skin inflammation.