Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1934437 | Biochemical and Biophysical Research Communications | 2008 | 6 Pages |
Abstract
Herein, we describe generation of the hCYP1A1_1A2_Cyp1a1/1a2(â/â)_Ahrd mouse line, which carries human functional CYP1A1 and CYP1A2 genes in the absence of mouse Cyp1a1 and Cyp1a2 genes, in a (>99.8%) background of the C57BL/6J genome and harboring the poor-affinity aryl hydrocarbon receptor (AHR) from the DBA/2J mouse. We have characterized this line by comparing it to our previously created hCYP1A1_1A2_Cyp1a1/1a2(â/â)_Ahrb1 line-which carries the same but has the high-affinity AHR of the C57BL/6J mouse. By quantifying CYP1A1 and CYP1A2 mRNA in liver, lung and kidney of dioxin-treated mice, we show that dose-response curves in hCYP1A1_1A2_Cyp1a1/1a2(â/â)_Ahrd mice are shifted to the right of those in hCYP1A1_1A2_Cyp1a1/1a2(â/â)_Ahrb1 mice-similar to, but not as robust as, dose-response curves in DBA/2J versus C57BL/6J mice. This new mouse line is perhaps more relevant than the former to human risk assessment vis-Ã -vis human CYP1A1 and CYP1A2 substrates, because poor-affinity rather than high-affinity AHR occurs in the vast majority of the human population.
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Authors
Zhanquan Shi, Ying Chen, Hongbin Dong, Robyn M. Amos-Kroohs, Daniel W. Nebert,