先天性输精管缺如（CAVD）是男性梗阻性无精子症及不育的重要病因，可合并囊性纤维病（CF）。CFTR是CAVD和CF共有的关键基因，但它导致CAVD的发病机制仍不清楚。我们前期研究发现CAVD患者群中新突变热点（Q1352H），该错义突变位于CFTR蛋白功能域，纯合子患者存在年龄依赖的梗阻进展。已证实CFTR编码的Cl离子通道蛋白可调控上皮细胞Na离子通道影响呼吸道黏液分泌及纤毛功能，是CF患者发生肺炎并进展为慢性阻塞性肺病的重要原因。因此我们推测：Q1352H错义突变可致Cl离子通道受损，Na离子重吸收增加，管腔黏液进行性稠厚，加重输精管梗阻导致CAVD发生。本研究拟通过体外细胞实验检测CFTR突变体（Q1352H）的表达定位和离子通道功能，及活体水平构建Q1352H突变小鼠，分析输精管内黏液和纤毛动态改变，阐明其对输精管缺如发生发展的分子机制，为此类患者的遗传诊断和治疗提供新理论依据。

Congenital absence of the vas deferens (CAVD) is one of the most important obstructive azoospermia in male infertility. It can be sporadic or one of the manifestations of cystic fibrosis (CF). CFTR is the pivotal gene shared by simplex CAVD and CF. However, the pathogenesis mechanism of CFTR-related CAVD remains unclear. In our previous study, we found a new mutation hotspot of CFTR (Q1352H) in a large population with simplex CAVD. Further follow-up studies revealed age-dependent obstructive progression in the CAVD patient with Q1352H homozygous mutation. The Cl ion channel encoded by CFTR gene can regulate epithelial Na ion channel (ENaC) and influence mucus secretion and cilium function in the respiratory tract, which is the most important factor in the pneumonia and chronic obstructive pulmonary disease (COPD) in CF patients. Therefore, we hypothesized that the missense mutation (Q1352H) could damage Cl ion channel and increase the absorption of Na ion, which lead to the obstruction of the vas deferens caused by the progressive thickening of mucus in the lumen. The above hypothesis is verified by detecting subcellular localization of the mutant CFTR (Q1352H) and cellular ion channels experiments in vitro, and further constructing Cftr-Q1352H knock-in mice model and analyzing dynamic changes of lumen mucus and cilium on the development of vas deferens in vivo. It will illuminate the molecular mechanism on the development of absence of vas deferens and provide novel theoretical basis for the genetic diagnosis and treatment of CFTR-related CAVD.