精子发生和成熟缺陷是导致雄性不育最主要的病因。课题组之前从人胰岛素瘤组织中克隆到一个新型分泌蛋白-INM02，并发现INM02参与了胰岛beta细胞功能的调控（Wang et al. J Endocrinol, 2009, 202: 355-364），课题组已成功建立了INM02基因剔除小鼠模型，表型分析发现INM02缺失导致雄性小鼠不育，进一步分析发现，INM02缺失的精子活力明显下降，体内和体外受精实验均表明，INM02缺失的精子不能使卵子受精，说明INM02缺失导致精子发生或成熟缺陷是引起雄性不育的病因。本项目以INM02对精子发生或成熟的调控为切入点，期望得到国家自然科学基金的资助，以INM02基因剔除雄性小鼠模型为研究对象，阐明INM02在精子发生或成熟过程中的作用及分子机制，推动雄性不育病因学的研究，进而发掘全新的治疗男性不育的药物靶点。

The defect of spermiogenesis and sperm maturation is the predominant cause of male infertility. In our previous study, a novel secreted protein, INM02, was cloned from a cDNA library of human insulinoma tissue and was proposed its involvement in the regulation of islet beta-cell function (Wang et al. J Endocrinol, 2009, 202: 355-364). We have successfully established INM02 knockout mouse model. Phenotype analysis indicated that INM02 deficiency resulted in male infertility. Extensive studies found that the motile ability of INM02-deficient sperm decreased significantly, and the sperm was unable to fertilize egg, suggesting that the defect of spermiogenesis or sperm maturation caused by INM02 deficiency contributed to male infertility. We hope to get support from NSFC and focus on the regulation of spermiogenesis or sperm maturation by INM02. In the future study, we will perform experiments on INM02 knockout male mouse model to elucidate the role and molecular mechanism of INM02 in spermiogenesis or sperm maturation, by which the pathogenesis of male infertility will be solidified and the novel drug target for treatment of male infertility will be discovered.