Humanized PXR-CAR Mouse

Humanized PXR-CAR Targeted Replacement Mouse Model
  • Cryopreserved
  • Mouse
  • Not available for direct purchase by CRO
Model No.NomenclatureGenotype
8223C57BL/6-Nr1i2tm1(NR1I2)Arte Nr1i3tm1(NR1I3)ArteInquire for genotype
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Overview

Nomenclature: C57BL/6-Nr1i2tm1(NR1I2)Arte Nr1i3tm1(NR1I3)Arte

  • This targeted mutation strain carries a replacement of the mouse Nr1i2 and Nr1i3 genes which encode for the nuclear receptors PXR and CAR with the corresponding human orthologous genes.
  • Useful in prediction of CYP induction and therefore pharmacokinetics, drug toxicity, and efficacy in man.
  • Model has relevance for the prediction of the hazard of non-genotoxic rodent liver growth carcinogens to humans.

Origin

The Humanized PXR-CAR Mouse was developed by Taconic in collaboration with CXR Biosciences. 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. 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 Humanized CAR Mouse model was created through a knock in of a human CAR construct containing the genomic sequence from the translational start site on exon 2 to exon 9 onto the ATG of murine CAR in C57BL/6NTac-derived ES cells. The expression of the human PXR and CAR receptors is driven by the corresponding mouse promoters. In both cases 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 selection markers. The Humanized PXR-CAR Mouse line was obtained by crossing the two single humanized mouse lines. Taconic received stock in 2008, and the line was embryo transfer derived. The colony was maintained by mating double homozygotes.

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