CMTM是我国科学家在国际上首次报道的新基因家族，已明确在免疫、肿瘤发生中有重要功能，且提示和男性生殖密切相关。其中CMTM2为睾丸特异表达基因，未有深入研究。申请人鉴定CMTM2与精子质量相关，构建了敲除小鼠表现不育表型，提示CMTM2为精子发生、精子质量相关关键分子。本课题拟通过综合分析临床男性不育标本CMTM2表达，确定CMTM2与男性不育相关性；通过精子功能实验和敲除小鼠模型，鉴定CMTM2作为关键节点分子参与男性生育的生物学过程；通过小鼠模型，细胞系等体内外实验确定CMTM2参与精子发生、精子功能调控的关键分子基础。最终从基础研究结合临床分析的角度诠释CMTM2参与精子发生、精子质量调控的相关性和分子机制。本课题为深入研究CMTM2在男性不育的功能和临床转化应用奠定科学基础；并为研究CMTM家族其它成员在男性生殖功能提供重要信息；为男性不育诊治或揭示某些男性不育病因提供线索。

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is a novel gene family that has been reported by Prof Han WenLing of Peaking university for the first time. They encode proteins that play important roles in the immune system, tumorigenesis, and the male reproductive system. Of them, CMTM2 is the testis-specific gene and its function in male fertility remains unclear. We current works implied that CMTM2 was related to sperm quality, and subsequence construction of Cmtm2b knockout mouse was performed, that demonstrated an infertility phenotype. All the current results indicated that CMTM2 was a promising molecule related to spermatogenesis and sperm quality regualtion. Here, we intend to determine the correlation between CMTM2 and male infertility by comprehensively analyzing the expression of CMTM2 in clinical male infertility specimens. By performing sperm function experiment and using knockout mouse model, we will identify key molecular processes of spermatogenesis and sperm quality regulation in which CMTM2 is involved. Through in vivo and in vitro experiments such as mouse model and cell line, we will study mechanism of CMTM2 involved in spermatogenesis and sperm function regulation. Finally, from the perspective of basic research combined with clinical analysis, the correlation and molecular mechanism of CMTM2 involved in spermatogenesis and sperm quality regulation will be interpreted. This project lays a scientific foundation for further research on the function and clinical application of CMTM2 in male infertility. It also provides important information for the study of the male reproductive function of other members of the CMTM family, and provides clues for the diagnosis and treatment of male infertility or reveal the cause of some male infertility.