A mouse containing firefly luciferase (fLUC) knocked into the mdr1a genomic locus allows noninvasive bioimaging of intestinal mdr1a gene expression in live animals. In the current study, we crossed mdr1a.fLUC mice into the pxr knockout (pxr−/−) genetic background and injected mice with pregnenolone-16α-carbonitrile (PCN), a strong mouse pregnane X receptor (PXR) ligand, and two therapeutically relevant taxanes, paclitaxel and docetaxel. All three agents induced mdr1a.fLUC expression (bioluminescence), but only PCN and docetaxel appeared to act primarily via PXR. These results demonstrate that the mdr1a.fLUC bioimaging model can capture changes in mdr1 gene expression under conditions of repeated xenobiotic treatment in vivo.
See article at J Pharmacol Exp Ther 2013, 345:438–445.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics