Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa

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Murine type VII collagen distorts outcome in human skin graft mouse model for dystrophic epidermolysis bullosa

Human skin graft mouse models are widely used to investigate and develop therapeutic strategies for the severe generalized form of recessive dystrophic epidermolysis bullosa (RDEB), which is caused by bi-allelic null mutations in COL7A1 and the complete absence of type VII collagen (C7). Most therapeutic approaches are focused on reintroducing C7. Therefore, C7 and anchoring fibrils are widely used as readouts in therapeutic research with skin graft models. In this study, we investigated the expression pattern of human and murine C7 in a grafting model, in which human skin is reconstituted out of in vitro cultured keratinocytes and fibroblasts. The model revealed that murine C7 was deposited in both human healthy control and RDEB skin grafts. Moreover, we found that murine C7 is able to form anchoring fibrils in human grafts. Therefore, we advocate the use of human-specific antibodies when assessing the reintroduction of C7 using RDEB skin graft mouse models. This article is protected by copyright. All rights reserved