- 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. Color:
Black Species:
Mouse Initial Publication:
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.
