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This targeted mutation strain carries a deletion of the mouse Nr1i2 gene which encodes for the nuclear receptor PXR.
Useful in defining the effect of PXR on CYP induction and therefore pharmacokinetics, drug toxicity, and efficacy.
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Origin: The Pxr Knockout mouse was developed by Taconic in collaboration with CXR Biosciences. It was generated by crossing a PXR humanized mouse line with a PhiC31 deleter mouse. The Humanized PXR Mouse model 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. 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. The Pxr Knockout Mouse model was derived from the Humanized PXR Mouse line through a PhiC31-mediated deletion of the human PXR sequence. Mouse exon 2, carrying the translational start site, is deleted in the knockout, while mouse exon 1 and exons 3-9 are still present. A splice acceptor polyA motif included in the targeting vector causes splicing of exon 1 to a polyA motif and thereby terminates the transcription. The absence of PXR protein was proven experimentally. Taconic received stock in 2009, and the line was embryo transfer derived. The colony is maintained by mating homozygotes.
Scheer N, Ross J, Rode A, Zevnik B, Niehaves S, Faust N, Wolf CR. (2008) A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response. J. Clin. Invest. 118(9): 3228-3239