This targeted mutation strain carries a replacement of the mouse aryl hydrocarbon receptor (Ahr) gene with the corresponding human orthologous gene.
Useful in prediction of CYP induction and therefore pharmacokinetics, drug toxicity, and efficacy in humans.
Origin: The Humanized AHR Mouse was developed by Taconic in collaboration with CXR Biosciences. It was created through a targeted replacement of mouse Ahr Exon 3 with a cDNA construct containing human AHR Exons 3-11 in C57BL/6NTac-derived ES cells. This leads to the expression of a fusion protein of amino acids encoded by mouse Exons 1 and 2 and human Exons 3 to 11 driven by the mouse Ahr promoter. The amino acids encoded by Exon 1 and 2 of mouse and human AHR are highly conserved, with only two changes in Exon 1. 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.
Initial Publication: Not published yet.