视神经脊髓炎(NMO)是青壮年常见的神经系统免疫相关性水通道蛋白病。尽管发病机制不详，但星形胶质（AS）细胞的水通道蛋白4（AQP4）及其抗体AQP4-IgG起关键作用。我们前期研究发现AQP4启动区及3'UTR区存在NMO易感的SNP位点，小样本分析表明3'UTR区rs1058424位点是导致NMO易感的关键因素，但作用机制不详。本项目拟结合基因测序和实验模型进一步研究：1）增加标本量，明确AQP4基因非编码区尤其是3'UTR区SNP对NMO易感性的影响；2）采用细胞及动物实验研究3'UTR区对AQP4异构体表达及正交排列结构（OAP）的调控作用；3）利用诱导多能干细胞（iPS）技术获得含有易感SNP患者的AS细胞，验证SNP与miRNA等对AQP4抗原表达及NMO发病的影响。本研究旨在阐明AQP4基因非编码区在NMO发病机制中的作用，为寻找NMO新的药物靶点奠定理论基础。

Neuromyelitis Optica (NMO) is an autoimmune water channel disease in the central nervous system (CNS) mainly involving the young adults. Despite of the unclarified underlying pathogenesis, aquaporin 4 (AQP4) protein on the membrane of the astrocytes (AS), and its antibody AQP4-IgG, have been suggested to play key roles in the pathogenesis of the disease. In our previous preliminary studies, we have found that the susceptible SNPs loci were present in both promoter regions and 3'UTR regions of the AQP4 gene. Furthermore, our study with small sample size has demonstrated that SNP rs1058424 locus might be the key predisposing factors leading to the pathogenesis of NMO. However, the mechanism of the relevant gene is still unknown. On this basis, we aimed to: 1) investigate the influence of non-coding region, especially the 3'UTR region, on the NMO susceptibility by increasing the sample size; 2) study the role of 3'UTR region on AQP4 antigen expression and NMO pathogenesis by in vitro cell experiment and in vivo animal experiment; 3) verify AQP4 gene functions using AS derived from induced pluripotent stem cells (iPS) in vitro. Our study will be helpful in confirming the role of AQP4 genes in the pathogenesis of NMO, also in finding a new drug target for NMO.