Nr2f2, also known as COUP-TF2, is a transcription factor belonging to the steroid thyroid hormone superfamily of nuclear receptors. It plays essential roles in various biological processes, including organogenesis, angiogenesis, and metabolism, and is expressed at high levels during mammalian development. It is involved in regulating many genes and pathways, such as progesterone signaling in the uterus [1].

In gene-knockout related studies, in Pgr-expressing cells of mouse uterus, ablation of Nr2f2 leads to reduced Hand2 expression, increased levels of Hand2 downstream effectors, and a suppressed progesterone signaling transcriptome [1]. In Wharton's Jelly stem cells, knockdown of Nr2f2 results in decreased expressions of Cyclin D1 and CDK4, slower cell proliferation, and increased expressions of IL6 and IL8 [2]. Also, in a family with congenital bicuspid aortic valve, a novel heterozygous loss-of-function mutation in Nr2f2 was identified, disrupting the synergistic transcriptional activation between Nr2f2 and GATA-4 [3].

In conclusion, Nr2f2 is crucial for normal development and physiological functions. Its disruption through gene knockout or mutation can lead to various disorders, including congenital heart diseases, uterine function abnormalities, and abnormal stem cell regulation. These findings from gene-knockout or knockdown models provide important insights into the role of Nr2f2 in different biological processes and disease conditions.