Ttc6, the tetratricopeptide repeat protein 6, is expressed mainly in the testes in mice. It plays a crucial role in maintaining male fertility and is likely involved in pathways related to sperm motility and flagellum structure [1].

A study on Ttc6 knockout mice demonstrated that the deletion of Ttc6 led to decreased sperm motility, an abnormal circular swimming pattern, and male subfertility [1]. Morphologically, spermatozoa showed an atypical hairpin-like appearance, and ultrastructurally, unsheathed flagella were observed at the midpiece-principal piece juncture. These findings suggest TTC6 is essential for maintaining the stability of the annulus region of the sperm flagellum, ensuring the rapid and directed motion of sperm [1]. In addition, TTC6 was proposed as a novel candidate gene in ciliopathies, and functional assays on patient-derived fibroblasts supported its role in this disorder [2].

In summary, Ttc6 is vital for male fertility in mice, mainly by ensuring the stability of the sperm flagellum annulus for proper sperm movement. The gene knockout mouse model has been instrumental in revealing Ttc6's role in male subfertility. Also, its proposed role in ciliopathies from functional studies indicates its potential significance in this disease area [1,2].

References:

1. Wang, Ziqi, Fang, Kailun, Wan, Yanling, Liu, Hongbin, Huang, Tao. 2023. TTC6-Mediated Stabilization of the Flagellum Annulus Ensures the Rapid and Directed Motion of Sperm. In Cells, 12, . doi:10.3390/cells12162091. https://pubmed.ncbi.nlm.nih.gov/37626901/

2. Shamseldin, Hanan E, Shaheen, Ranad, Ewida, Nour, Seidahmed, Mohammed Zain, Alkuraya, Fowzan S. 2020. The morbid genome of ciliopathies: an update. In Genetics in medicine : official journal of the American College of Medical Genetics, 22, 1051-1060. doi:10.1038/s41436-020-0761-1. https://pubmed.ncbi.nlm.nih.gov/32055034/