POU3F2, also known as Brn2, is a transcription factor mainly expressed in the central nervous system and plays a crucial role in brain development [4]. It contains mammal-specific base sequences encoding three stretches of homopolymeric amino acids. POU3F2 is associated with multiple biological pathways, and its dysregulation is linked to various diseases. Genetic mouse models, such as KO or CKO models, are valuable for studying its functions.

In Pou3f2⊿ mice, there are deficits in reproductive performance and maternal behavior, with impaired exploratory and pup-retrieval behaviors in females [2]. Pou3f2Δ/Δ mice, where homopolymeric amino acid repeats are deleted, show cognitive impairment in object recognition and location tests, along with decreased adult hippocampal neurogenesis [4]. In cancer research, high expression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation by interacting with ARNT2 [1]. In glioblastoma, integrin α3 regulates stemness and invasion through POU3F2 [5], and a miR-146a-POU3F2/SMARCA5 pathway is important for suppressing GBM-stemness [7]. Also, POU3F2 is a risk factor for schizophrenia, regulating TRIM8 expression through an SCZ-associated SNP, and both genes may be involved in SCZ etiology [3]. Moreover, monoallelic intragenic POU3F2 variants lead to neurodevelopmental delay and hyperphagic obesity [6].

In conclusion, POU3F2 is essential for normal brain function, including cognitive function and adult hippocampal neurogenesis. Its role in maternal behavior in mice also highlights its importance in mammalian-specific behaviors. In diseases, POU3F2 is involved in cancer (such as breast and brain cancers) and neuropsychiatric disorders like schizophrenia and neurodevelopmental disorders with obesity. The study of POU3F2 using KO/CKO mouse models has significantly contributed to understanding its functions in these biological processes and disease conditions.