Adad2, Adenosine deaminase domain containing 2, is a testis-specific protein composed of a double-stranded RNA binding domain and a non-catalytic adenosine deaminase domain. It is essential for male reproduction, playing key roles in spermiogenesis and piRNA biogenesis [1]. Genetic mouse models, such as KO mouse models, are valuable tools for studying Adad2's functions.

In mouse models, deletion of Adad2 causes male-specific sterility due to abnormal spermiogenesis. Adad2 interacts with multiple RNA-binding proteins involved in piRNA biogenesis like MILI, MIWI, RNF17, and YTHDC2. It co-localizes and forms novel granules with RNF17 in spermatocytes. Ablation of Adad2 impairs RNF17 granule formation, decreases cluster-derived pachytene piRNAs, and increases ping-pong-derived piRNAs [1]. Also, Adad2 is required for the translation of Mdc1, a key regulator of XY-body formation in meiotic male germ cells. Loss of Adad2 leads to normal establishment but failed maintenance of the XY-body, abnormal autosomal heterochromatin, and ultimately post-meiotic germ cell heterochromatin perturbation and cell death [2].

In conclusion, Adad2 is crucial for male germ cell development. Through model-based research, especially KO mouse models, we've learned that Adad2 is essential for spermiogenesis, piRNA biogenesis, and the regulation of heterochromatin in male germ cells. Its disruption causes male infertility, highlighting its significance in understanding male reproductive diseases [1,2,3].

References:

1. Lu, Yonggang, Nagamori, Ippei, Kobayashi, Hisato, Matzuk, Martin M, Ikawa, Masahito. 2023. ADAD2 functions in spermiogenesis and piRNA biogenesis in mice. In Andrology, 11, 698-709. doi:10.1111/andr.13400. https://pubmed.ncbi.nlm.nih.gov/36698249/

2. Chukrallah, Lauren G, Badrinath, Aditi, Vittor, Gabrielle G, Snyder, Elizabeth M. 2022. ADAD2 regulates heterochromatin in meiotic and post-meiotic male germ cells via translation of MDC1. In Journal of cell science, 135, . doi:10.1242/jcs.259196. https://pubmed.ncbi.nlm.nih.gov/35191498/

3. Shi, Baolu, Shah, Wasim, Liu, Li, Yuan, Yan, Shi, Qinghua. 2023. Biallelic mutations in RNA-binding protein ADAD2 cause spermiogenic failure and non-obstructive azoospermia in humans. In Human reproduction open, 2023, hoad022. doi:10.1093/hropen/hoad022. https://pubmed.ncbi.nlm.nih.gov/37325547/