This targeted mutation strain carries a replacement of the mouse Nr1i3 gene which encodes for the nuclear receptor CAR with the corresponding human orthologous gene.
Useful in prediction of CYP induction and therefore pharmacokinetics, drug toxicity, and efficacy in humans.
Origin: The Humanized CAR Mouse was developed by Taconic in collaboration with CXR Biosciences. It 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 CAR receptor is driven by the mouse Car promoter. 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. 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