Adad2, Adenosine deaminase domain containing 2, is a testis-specific protein with a double-stranded RNA binding domain and a non-catalytic adenosine deaminase domain. It is essential for male reproduction, functioning in pathways related to spermiogenesis and piRNA biogenesis. Mouse models have been crucial in studying its functions [1,4].

In mouse models, deletion of Adad2 leads to male-specific sterility due to abnormal spermiogenesis [1]. Adad2 interacts with multiple RNA-binding proteins involved in piRNA biogenesis like MILI, MIWI, RNF17, and YTHDC2. Ablation of Adad2 impairs the formation of RNF17 granules, decreases cluster-derived pachytene piRNAs, and increases ping-pong-derived piRNAs [1]. Also, Adad2 mutants show defective translation of Mdc1 late in meiosis, resulting in abnormal maintenance of the XY-body, autosomal heterochromatin perturbations, and post-meiotic germ cell death [2]. Biallelic mutations in Adad2 in humans and mice disrupt the differentiation of round spermatids to spermatozoa, causing azoospermia [3].

In summary, Adad2 is vital for male fertility, with its functions in spermiogenesis and piRNA biogenesis being revealed through mouse gene knockout models. These models have also shown its importance in maintaining proper heterochromatin structure during male germ cell development, highlighting its role in male-specific infertility-related diseases.