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This targeted mutation strain carries a replacement of the mouse Nr1i2 gene which encodes for the nuclear receptor PXR with the corresponding human orthologous gene.
Useful in prediction of CYP induction and therefore pharmacokinetics, drug toxicity, and efficacy in humans.
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Origin: The Humanized PXR Mouse was developed by Taconic in collaboration with CXR Biosciences. It was created through a knock in of a human PXR cDNA/genomic construct onto the ATG of murine Pxr in C57BL/6NTac-derived ES cells. The human PXR sequence that was introduced contains a cDNA fusion of exon 2-4, intron 4, exon 5, intron 5, exon 6, intron 6, exon 7, intron 7, and cDNA fusion exon 8 + 9. The expression of the human PXR receptor is driven by the mouse Pxr promoter. Targeted ES cells were injected into BALB/cJBomTac blastocysts and the resultant chimeras were backcrossed to a Flpe deleter strain on C57BL/6J to eliminate the selection marker. Taconic received stock in 2009, and the line was embryo transfer derived. The colony is maintained by mating homozygotes.
Scheer N, Ross J, Kapelyukh Y, Rode A, Wolf CR. (2010). In vivo
responses of the human and murine pregnane X receptor to dexamethasone in mice. DMD 38(7): 1046-1053