• Background strain: Sprague Dawley
• Biallelic 10 bp deletion within Nr1i3 gene
• Biallelic 20 bp deletion within Nr1i2 gene

Availability: Live colony
Zygosity: Homozygous

PXR and CAR are involved in the induction of cytochrome p4503A (Cyp3a) and is abundantly expressed in the liver and intestine. This model is useful for studying metabolism of xenobiotic compounds and hepatotoxicity.

This double knockout model was generated by crossing together the single PXR and Car knockout rat lines.The activation of nuclear receptors, including the Pregnane X Receptor (PXR) and the Constitutive Androstane Receptor (CAR), is a common Mode of Action (MoA) for chemicals that exhibit non-genotoxic hepatocarcinogenicity in rodents. Conversely, the activation of the human PXR and/or CAR receptors is not believed to result in a carcinogenic response. Therefore, if a compound causes liver tumors in rodents, or if studies demonstrate that the compound is a nuclear receptor agonist, it is critical to unambiguously demonstrate the role of specific nuclear receptors in the rodent response, for example by using PXR or CAR KO rats. CXR has extensive experience of working with global pharmaceutical, chemical and agrochemical companies to demonstrate the absence of human relevance for nuclear-receptor mediated carcinogenicity.