The dominantly inherited form of dystrophic epidermolysis bullosa (DDEB), a mechano-bullous disease which presents blister with formation in the skin, is the result of dominant negative mutations in the type VII collagen gene (COL7A1). These mutations cause conformational changes in type VII collagen that interfere with the proper assembly of anchoring fibrills, important attachment structures of the cutaneous basement membrane zone. Currently, there is no available treatment option nor applicable in vivo experimental model for DDEB.
The aim of the proposed research is to establish an animal model for DDEB by expressing a type VII collagen construct in mice, that carries dominant negative mutations designed on the basis of COL7Al mutations in human DDEB patients. The in vivo models will be used to evaluate the feasibility of a novel treatment option, consisting of the utilization of hammerhead ribozymes to selectively eliminate mutant mRNA. The restoration of the normal phenotype will be followed using a number of qualitative and quantitative methods.
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