Tg(EEF1A1-Ahr*)1Pjvt

Mice bearing this transgene express the major, "insertion" variant of the aryl-hydrocarbon receptor (AHR) of Han/Wistar rats, which are exceptionally resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) acute toxicity. In Han/Wistar rats, this aberrant receptor, in which the normal 38 C-terminal amino acids are replaced by seven novel amino acids, is translated from two of the three mis-spliced mRNAs resulting from a point mutation in the first nucleotide of intron 10. The transgene contains the promoter of the human eukaryotic translation elongation factor-1alpha1 (EEF1A1, also called "EF1alpha") followed by a 200 bp intron, a ~90 bp fusion of most of the mouse Ahr leader sequence with the 30-bp UTR of the rat Ahr mRNA, a cDNA encoding the Han/Wistar rat "insertion" AHR variant, the SV40 late polyadenylation signal, and nearly 800 bp of rat Ahr 3' UTR; this entire construct is flanked 5' by a 600 bp and 3' by a 250 bp chicken beta-globin core insulator. It was estimated by real-time quantitative polymerase chain reaction (qPCR) analysis that 30 copies of the transgene are present per haploid genome. Transgene-derived mRNA is present in every one of multiple tissues analyzed by reverse transcription-PCR (RT-PCR) and has been shown to be inducible by orally administered TCDD in the liver, where the rat protein also has been detected by western blot analysis. (J:147952)