CFAP69, or cilia and flagella-associated protein 69, is crucial for cilia-and flagella-related functions. It is involved in pathways related to sperm flagella formation and olfactory transduction. In sperm, it is essential for flagellum assembly/stability, and in the olfactory system, it regulates olfactory transduction kinetics [3].

Multiple studies, including the generation of Cfap69 knockout mouse models, have demonstrated its significance. Homozygous loss-of-function mutations in Cfap69 in both humans and mice lead to asthenoteratospermia with multiple morphological abnormalities of the sperm flagella (MMAF), a severe form of sperm defect causing male infertility. Sperm from Cfap69 knockout mice recapitulate the MMAF phenotype, with ultrastructural analysis showing severe disruption of flagellum structure, while spermatogenesis overall progression is preserved [1,2].

In conclusion, Cfap69 is essential for proper flagellum formation in sperm and for regulating olfactory transduction kinetics. The Cfap69 knockout mouse models have been instrumental in revealing its role in male infertility caused by MMAF, providing insights into the molecular mechanisms underlying this condition and potential implications for genetic diagnosis, counseling, and treatment [1,2].

References:

1. He, Xiaojin, Li, Weiyu, Wu, Huan, Zhang, Feng, Cao, Yunxia. 2018. Novel homozygous CFAP69 mutations in humans and mice cause severe asthenoteratospermia with multiple morphological abnormalities of the sperm flagella. In Journal of medical genetics, 56, 96-103. doi:10.1136/jmedgenet-2018-105486. https://pubmed.ncbi.nlm.nih.gov/30415212/

2. Dong, Frederick N, Amiri-Yekta, Amir, Martinez, Guillaume, Zhao, Haiqing, Coutton, Charles. . Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse. In American journal of human genetics, 102, 636-648. doi:10.1016/j.ajhg.2018.03.007. https://pubmed.ncbi.nlm.nih.gov/29606301/

3. Talaga, Anna K, Dong, Frederick N, Reisert, Johannes, Zhao, Haiqing. 2017. Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction Kinetics in Mice. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 37, 5699-5710. doi:10.1523/JNEUROSCI.0392-17.2017. https://pubmed.ncbi.nlm.nih.gov/28495971/