Arnt2, short for aryl hydrocarbon receptor nuclear translocator 2, is a basic-helix-loop-helix (bHLH) transcription factor belonging to the bHLH PAS family. It is involved in multiple biological processes such as neuronal development, axonal health, and cell fate determination in the hemato-vascular system. In the nervous system, it participates in activity-dependent gene expression regulation and may be linked to neuropsychiatric conditions related to empathy [1,4].

In mouse models, disruption of Arnt2 expression in the anterior cingulate cortex reduces affect sharing, a form of affective empathy. Selective Arnt2 ablation in somatostatin-expressing interneurons leads to abnormal neural activities in the ACC, resulting in reduced vicarious freezing [1]. In zebrafish, arnt1;arnt2 double mutant embryos lack blood cells and most endothelial cells, suggesting Arnt2's role in hemato-vascular specification [2]. In cancer research, in vitro and in vivo studies show that Arnt2 may act as a tumor suppressor. For example, in oral squamous cell carcinoma, overexpression of Arnt2 decreases cellular proliferation [3]. Similar results are seen in gastric cancer, non-small cell lung cancer, and glioblastoma [5,6,7].

In conclusion, Arnt2 is crucial for neuronal development, hemato-vascular specification, and may play a role in regulating cancer cell growth. Mouse models, especially gene knockout (KO) and conditional knockout (CKO) models, have been instrumental in uncovering Arnt2's functions in areas such as empathy-related neuropsychiatric conditions and cancer biology.