Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3 localization and male fertility in mice

Chemokines are signaling proteins that are secreted to induce chemotaxis during immunological events. However, the functions of transmembrane-type chemokine-like factor (CKLF) and the protein family CMTM (CKLF-like MARVEL transmembrane domain containing) remain to be determined. In this study, we focused on the testis-specific mouse Cmtm gene cluster ( Cmtm1 , Cmtm2a , and Cmtm2b ) and generated CRISPR/Cas9-mediated mutant mice to examine its physiological functions. Although Cmtm1 mutant mice were fertile, Cmtm2a and Cmtm2b double mutant mice had defects in male fertility due to impaired sperm function. We found that co-expression of sperm membrane proteins CMTM2A and CMTM2B is required for male fertility and affects the localization of the sperm membrane protein ADAM3 in regulating sperm fertilizing ability.