- This targeted mutation strain carries a deletion of the mouse Nr1i3 gene which encodes for the nuclear receptor CAR.
- Useful in defining the effect of CAR on CYP induction and therefore pharmacokinetics, drug toxicity, and efficacy.
Origin: The Car Knockout mouse was developed by Taconic in collaboration with CXR Biosciences. It was generated by crossing a CAR humanized mouse line (Model 9101) with a PhiC31 deleter mouse. 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. 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 Car Knockout Mouse model was derived from the Humanized CAR Mouse line through a PhiC31-mediated deletion of the human CAR sequence. This deletes all exons coding for functional domains of CAR (exons 3-9). The absence of CAR protein was proven experimentally. Taconic received stock in 2009, and the line was embryo transfer derived. The colony was 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