Ccdc38, the coiled-coil domain-containing 38 gene, is a testes-specific gene in mice, and its protein product is conserved in various mammalian species [2]. It is mainly expressed in spermatogonia and spermatocytes. Functionally, it is involved in sperm flagellum biogenesis, which is essential for male fertility [1].

In male mice with Ccdc38 inactivation, the manchette is distorted, spermatozoa flagella show multiple morphological abnormalities, and eventually, male sterility occurs [1]. Ccdc38 interacts with CCDC42, localizing on the manchette and sperm tail during spermiogenesis [1]. It also interacts with intraflagellar transport protein 88 (IFT88) and outer dense fibrous 2 (ODF2), and Ccdc38 knockout reduces the transport of ODF2 to the flagellum [1]. Additionally, Ccdc38-KO sperm display acrosomal hypoplasia and typical multiple morphological abnormalities of the flagella (MMAF) phenotypes, with disorganized fibrous sheaths [3].

In conclusion, Ccdc38 is crucial for sperm flagellum biogenesis and acrosome biogenesis in mice, as demonstrated by gene-knockout mouse models. These findings suggest that Ccdc38 mutations might be associated with male infertility in humans, providing valuable insights into understanding the molecular mechanisms of male infertility [1,3].

References:

1. Zhang, Ruidan, Wu, Bingbing, Liu, Chao, Yuan, Li, Li, Wei. 2022. CCDC38 is required for sperm flagellum biogenesis and male fertility in mice. In Development (Cambridge, England), 149, . doi:10.1242/dev.200516. https://pubmed.ncbi.nlm.nih.gov/35587122/

2. Lin, Shou-Ren, Li, Yu-Chi, Luo, Man-Ling, Jiang, Zhi-Mao, Gui, Yao-Ting. 2016. Identification and characteristics of the testes-specific gene, Ccdc38, in mice. In Molecular medicine reports, 14, 1290-6. doi:10.3892/mmr.2016.5360. https://pubmed.ncbi.nlm.nih.gov/27278724/

3. Wang, Yaling, Huang, Xueying, Sun, Guoying, Li, Jinsong, Wang, Lingbo. 2023. Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice. In Journal of genetics and genomics = Yi chuan xue bao, 51, 407-418. doi:10.1016/j.jgg.2023.09.002. https://pubmed.ncbi.nlm.nih.gov/37709195/