Ak8-KO Mouse

Ak8, an adenylate kinase, is crucial for efficient intracellular ATP transfer. It belongs to Subgroup III AKs, which are unique to the male reproductive system and conserved across chordates. Adenylate kinases are involved in maintaining adenine nucleotide homeostasis, an essential process for numerous cellular functions [1].

In knockout mouse models, Ak8 was found to be indispensable for male reproduction as it is central to promoting sperm motility. Ak8 interacts with the radial spoke (RS) of the axoneme, and together with Ak9, it cooperatively regulates ATP transfer in the axoneme, being concentrated at energy-consuming sites in the flagellum [1]. In addition, in Cfap45-deficient mice, microtubule sliding of dyskinetic sperm can be rescued with the addition of AMP or ADP along with ATP, suggesting a role of Ak8 in an adenine nucleotide homeostasis module associated with CFAP45 in ciliary and flagellar beating [2].

In conclusion, Ak8 plays a vital role in male reproduction, particularly in sperm motility, by regulating ATP transfer in the flagellar axoneme. The use of knockout mouse models has been instrumental in revealing these functions, which are relevant to understanding male infertility, a disease area where Ak8's role provides important insights into the underlying mechanisms [1,2].

References:

1. Wu, Huan, Zhang, Yanman, Li, Yuqian, Liu, Mingxi, He, Xiaojin. 2024. Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes. In Science China. Life sciences, 67, 1697-1714. doi:10.1007/s11427-023-2539-1. https://pubmed.ncbi.nlm.nih.gov/38761355/

2. Dougherty, Gerard W, Mizuno, Katsutoshi, Nöthe-Menchen, Tabea, Hamada, Hiroshi, Omran, Heymut. 2020. CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module. In Nature communications, 11, 5520. doi:10.1038/s41467-020-19113-0. https://pubmed.ncbi.nlm.nih.gov/33139725/