ACTL9, also known as actin-like 9, is a gene that plays a crucial role in male reproductive processes. It is involved in the formation and maintenance of sperm structure, specifically in the assembly of the flagellum and the arrangement of the mitochondrial sheath in spermatozoa. These functions are essential for sperm motility and fertilization, highlighting its overall biological importance in reproduction [1]. Genetic mouse models have been valuable tools for studying ACTL9's function in vivo [1,2].

In a study on Actl9-mutated mouse models, abnormal Computer-assisted sperm analysis (CASA) parameters were observed, along with irregular '9 + 2' structures in flagella, indicating a disrupted flagellum assembly [1]. Homozygous pathogenic variants in ACTL9 in humans led to abnormal ultrastructure of the perinuclear theca (PT), mislocalization of PLCζ in sperm, failed normal calcium oscillations in oocytes, and total fertilization failure (TFF) [2]. These findings were further confirmed in the Actl9-mutated mouse model, which also showed TFF [2].

In conclusion, ACTL9 is essential for proper sperm structure and function, specifically in flagellum assembly, mitochondrial sheath arrangement, and the localization of proteins crucial for oocyte activation. The Actl9-mutated mouse models have significantly contributed to understanding its role in male infertility and fertilization failure, providing insights into the genetic mechanisms underlying these reproductive issues [1,2].

References:

1. Li, Qi, Huang, Yilian, Zhang, Shen, Lin, Ge, Dai, Jing. 2024. Homozygous ACTL9 mutations cause irregular mitochondrial sheath arrangement and abnormal flagellum assembly in spermatozoa and male infertility. In Journal of assisted reproduction and genetics, 41, 2271-2278. doi:10.1007/s10815-024-03171-0. https://pubmed.ncbi.nlm.nih.gov/38963606/

2. Dai, Jing, Zhang, Tianlei, Guo, Jing, Zheng, Wei, Lin, Ge. 2021. Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice. In American journal of human genetics, 108, 469-481. doi:10.1016/j.ajhg.2021.02.004. https://pubmed.ncbi.nlm.nih.gov/33626338/