Axin2, also known as Conductin, is a key inhibitory molecule in the Wnt signaling pathway [1,2,3,4,5,6]. The Wnt pathway is crucial for maintaining and differentiating many tissues, controlling cell proliferation, cytometaplasia, migration, and apoptosis [6]. Axin2's role has been studied using various genetic models, including KO and CKO mouse models, which help reveal its function in specific biological processes and disease conditions.

In ASD mouse models (Shank3 -/- and valproic acid-treated mice), aberrant activation of canonical Wnt signaling was observed. Axin2 interacts with the glycolytic enzyme enolase 1 (ENO1) in ASD neurons. The Axin2 stabilizer XAV939 blocked the Axin2/ENO1 interaction, rescued synaptic and social phenotypes, indicating Axin2 as a potential therapeutic target for ASD-related social dysfunction [1]. In colorectal cancer, Axin2 is constitutively activated. A small-molecule compound CW85319 enhanced Axin2's interaction with GSK3β, promoting Axin2 phosphorylation, ubiquitination, and degradation, and suppressing CRC growth and metastasis [3]. In macrophages, Axin2 depletion alleviated senescence and increased immune response after myocardial infarction, suggesting it as a novel therapeutic strategy post-MI [7].

In conclusion, Axin2 plays essential roles in regulating Wnt signaling-related biological functions. Mouse models, especially KO/CKO models, have been instrumental in uncovering Axin2's role in diseases such as autism spectrum disorders, colorectal cancer, and post-myocardial infarction conditions, providing potential therapeutic targets for these diseases.