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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.
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Useful in prediction of CYP induction and therefore pharmacokinetics, drug toxicity, and efficacy in humans.
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 was maintained by mating homozygotes. Color:
Black Species:
Mouse Initial Publication:
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.
