Cfap52, also known as WDR16, is a protein-coding gene. It is a centrosome/basal body protein and localizes to the manchette and the flagellum in male germ cells [3]. It is implicated in motile cilia-related functions and plays a role in the development of spermatozoa, which is crucial for male fertility [3].

In male infertility research, whole-exome sequencing identified compound heterozygous mutations in CFAP52 that recessively cosegregated with male infertility status in a non-consanguineous Chinese family. Spermatozoa of the CFAP52-mutant patient showed abnormal head-tail connection and deformed flagella. Cfap52-knockout mice resembled the human infertile phenotype, with a mixed acephalic spermatozoa syndrome and multiple morphological abnormalities of the sperm flagella. Ultrastructural analyses revealed a failure of connecting piece formation and a disorder of the '9 + 2' axoneme structure. CFAP52 interacts with SPATA6, essential for its stability, and CFAP52 deficiency reduces the expression of microtubule inner proteins and radial spoke proteins. Also, Cfap52-associated male infertility in humans and mice could be overcome by intracytoplasmic sperm injection [1]. In another study, Cfap52 knockout in mice led to decreased sperm motility due to disorganization of the mid-piece-principal piece junction of the sperm tail, and it interacted with CFAP45, with Cfap52 knockout decreasing the expression level of CFAP45 in sperm flagellum and disrupting microtubule sliding [2].

In conclusion, Cfap52 is essential for sperm development and motility, playing a crucial role in male fertility. The Cfap52 knockout mouse models have significantly contributed to understanding the mechanisms underlying male infertility related to sperm head-tail connection and flagella development defects [1,2].

References:

1. Jin, Hui-Juan, Ruan, Tiechao, Dai, Siyu, Shen, Ying, Chen, Su-Ren. 2023. Identification of CFAP52 as a novel diagnostic target of male infertility with defects of sperm head-tail connection and flagella development. In eLife, 12, . doi:10.7554/eLife.92769. https://pubmed.ncbi.nlm.nih.gov/38126872/

2. Wu, Bingbing, Li, Rachel, Ma, Shuang, Sun, Ling, Yuan, Li. 2023. The cilia and flagella associated protein CFAP52 orchestrated with CFAP45 is required for sperm motility in mice. In The Journal of biological chemistry, 299, 104858. doi:10.1016/j.jbc.2023.104858. https://pubmed.ncbi.nlm.nih.gov/37236356/

3. Tapia Contreras, Constanza, Hoyer-Fender, Sigrid. 2020. The WD40-protein CFAP52/WDR16 is a centrosome/basal body protein and localizes to the manchette and the flagellum in male germ cells. In Scientific reports, 10, 14240. doi:10.1038/s41598-020-71120-9. https://pubmed.ncbi.nlm.nih.gov/32859975/