Nr1i2-flox Mouse

Nr1i2, also known as the pregnane X receptor (PXR), is a nuclear receptor classified as a xenoreceptor. It is activated by various xenobiotics, including drugs, and regulates the transcription level of major drug-metabolizing enzymes and transporters, facilitating xenobiotic elimination from the body [1]. It also has a role in the regulation of intestinal inflammation and fibrosis, and is involved in maintaining mucosal integrity [2,3].

In fibrotic complications of inflammatory bowel diseases (IBDs), Nr1i2-deficient mice showed exacerbated fibrosis after DSS-induced colitis, with greater neutrophil infiltration and innate cytokine production compared to wild-type mice. Deletion of PXR in fibroblasts, but not the epithelium, recapitulated this phenotype [2]. In addition, Nr1i2-deficient myofibroblasts were hyperresponsive to stimulation, producing increased levels of inflammatory mediators [2].

In conclusion, Nr1i2 plays a crucial role in drug metabolism and in regulating intestinal inflammation and fibrosis. Studies using Nr1i2-deficient mouse models have revealed its significance in the development of fibrotic complications in IBDs, highlighting its potential as a therapeutic target in such disease areas.