Protein encoded by Nr1i2 (nuclear receptor subfamily 1, group I, member 2; also called PXR, pregnane X receptor) regulates genes that encode various types of enzymes and transporters in drug metabolism and disposition. It also directly binds transcription factors that co-regulate hepatic genes encoding enzymes for glucose or lipid metabolism, and regulates the expression of estrogen sulfotransferase SULT1E1 (sulfotransferase family 1E, member 1) in mouse livers and human hepatoma-derived cells. Evidence indicates that phosphorylated NR1I2/PXR functions as a transcriptional repressor to the SULT1E1/Sult1e1 gene in human liver cells and mouse livers. These PXR S347A KI knock-in mice carry a CRISPR/Cas9-generated S347A phosphorylation site mutation in the mouse Nr1i2 gene. Fasting-induced expression of SULT1E1 (sulfotransferase family 1E, member 1) in the liver is increased in homozygous PXR S347A KI mice compared with wildtype animals. Expression levels of the mutant protein are comparable to those of the wildtype.

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PXR S347A KI knock-in mice carry a CRISPR/Cas9-generated S347A phosphorylation site mutation in the mouse Nr1i2 (nuclear receptor subfamily 1, group I, member 2; also called PXR, pregnane X receptor) gene. Fasting-induced expression of SULT1E1 (sulfotransferase family 1E, member 1) in the liver is increased in homozygous PXR S347A KI mice compared with wildtype animals.

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