Oas2-KO Mouse

Oas2, short for 2'-5'-oligoadenylate synthetase 2, is an interferon (IFN)-induced antiviral enzyme. It belongs to the OAS family, which also includes OAS1, OAS3, and OAS-like (OASL). Oas2 can generate 2'-5'-linked oligoadenylates upon activation by double-stranded RNA, which is involved in the RNA cleavage pathway and antiviral response system [6,8].

In breast cancer, high Oas2 mRNA expression is associated with favorable prognosis, potentially making it a prognostic biomarker [1]. In psoriasis, Oas2 is overexpressed in lesional skin and serum, and its expression is downregulated by biologics. Silencing Oas2 inhibits keratinocyte proliferation by regulating the cell cycle and suppressing IFN-1-induced phosphorylation of Jak1 and signal transducer and activator of transcription 1, suggesting it may be a therapeutic biomarker [2]. In SARS-CoV-2-related multisystem inflammatory syndrome in children, autosomal recessive deficiencies of Oas2 lead to excessive production of inflammatory cytokines upon viral stimulation, underlying the disease mechanism [3]. In mammary cancer, an activating mutation in Oas2 prevents pregnancy-driven metastases and enhances the effectiveness of checkpoint immunotherapy, establishing it as a therapeutic target [4]. In testicular cancer, upregulating Oas2 by piR-36249 and DHX36 inhibits cancer cell progression [5]. Oas2 also restricts intracellular Mycobacterium tuberculosis replication and enhances pro-inflammatory cytokine secretion [6], and inhibits Zika virus replication through activation of the Type Ι IFN signaling pathway [7].

In conclusion, Oas2 plays crucial roles in multiple disease conditions, including cancer, psoriasis, and infectious diseases. Its functions in these diseases range from being a prognostic biomarker, a therapeutic target, to being involved in the regulation of cell proliferation, cytokine production, and antiviral responses. Studies, especially those with potential loss-of-function models, have significantly contributed to our understanding of Oas2's role in these biological processes and disease conditions.