| First Author | Shi Z | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 376 |
| Issue | 4 | Pages | 775-80 |
| PubMed ID | 18814841 | Mgi Jnum | J:141523 |
| Mgi Id | MGI:3818568 | Doi | 10.1016/j.bbrc.2008.09.068 |
| Citation | Shi Z, et al. (2008) Generation of a 'humanized' hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahrd mouse line harboring the poor-affinity aryl hydrocarbon receptor. Biochem Biophys Res Commun 376(4):775-80 |
| abstractText | Herein, we describe generation of the hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahr(d) 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(-/-)_Ahr(b1) 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(-/-)_Ahr(d) mice are shifted to the right of those in hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahr(b1) 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-a-vis human CYP1A1 and CYP1A2 substrates, because poor-affinity rather than high-affinity AHR occurs in the vast majority of the human population. |
