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

隐性营养不良大疱性表皮松解症包括一组由VII型胶原基因（COL7A1）突变引起的遗传性大疱性疾病，COL7A1是锚定纤维的主要成分。我们利用转基因拯救实验研究了在表皮角质形成细胞或真皮成纤维细胞中表达人类Col7a1的Col7a1敲除小鼠中锚定纤维的形成。在两种救援小鼠中，基底膜区均可见正常的锚定纤维形成。这些数据表明，我们可以选择角化细胞或成纤维细胞作为大疱性表皮松解症基因治疗的靶细胞。此外，使用相同的转基因救援实验，我们能够产生具有突变的人类COL7A1基因的大疱性表皮松解症存活动物模型。该模型对进一步研究大疱性表皮松解症的发病机制和开发大疱性表皮松解症的基因治疗具有很大的潜力。

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.