@article {Zhang2022.01.10.475757, author = {Ruidan Zhang and Bingbing Wu and Chao Liu and Xiuge Wang and Liying Wang and Sai Xiao and Yinghong Chen and Huafang Wei and Fei Gao and Li Yuan and Wei Li}, title = {Ccdc38 is required for sperm flagellum biogenesis and male fertility in mouse}, elocation-id = {2022.01.10.475757}, year = {2022}, doi = {10.1101/2022.01.10.475757}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Sperm flagellum is essential for male fertility, defects in flagellum biogenesis are associated with male infertility. Deficiency of CCDC42 is associated with malformation of the mouse sperm flagella. Here, we find that the testis-specific expressed protein CCDC38 (coiled-coil domain containing 38) interacts with CCDC42 and localizes on manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in distorted manchette, multiple morphological abnormalities of the flagella (MMAF) of spermatozoa, and eventually male sterility. Furthermore, we find that CCDC38 interacts with intra-flagellar transport protein 88 (IFT88) as well as the outer dense fibrous 2 (ODF2), and its depletion reduces the transportation of ODF2 to flagellum. Altogether, our results uncover the essential role of CCDC38 during sperm flagellum biogenesis, and suggesting the defects of these genes might be associated with male infertility in human being.Summary statement We demonstrated that CCDC38, localizes on manchette and sperm tail, is crucial for male fertility.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2022/01/11/2022.01.10.475757}, eprint = {https://www.biorxiv.org/content/early/2022/01/11/2022.01.10.475757.full.pdf}, journal = {bioRxiv} }