Analysis of the gene therapy for epidermolysis bullosa using transgenic rescue experiments of the disease model mice

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Recessive dystrophic epidermolysis bullosa comprises a group of hereditary bullous disease caused by mutations in the type VII collagen gene (COL7A1) that is a major component of anchoring fibril. We have investigated anchoring fibril formation in the Col7a1 knockout mice that express human COL7A1 in epidermal keratinocytes or dermal fibroblasts, using transgenic rescue experiments. In both rescue mice, normal anchoring fibril formation was seen within basement membrane zone. These data indicate that we can select either keratinocytes or fibroblasts as target cells in case of gene therapy for epidermolysis bullosa. Furthermore, using same transgenic rescue experiments, we were able to generate surviving animal models of epidermolysis bullosa with mutated human COL7A1 gene. This model has great potential for future research into the pathomechanisms of epidermolysis bullosa and the development of gene therapies for epidermolysis bullosa patients.