ToxSci Advance Access originally published online on July 20, 2005
Toxicological Sciences 2005 87(2):529-536; doi:10.1093/toxsci/kfi260
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Coplanar Polychlorinated Biphenyls Activate the Aryl Hydrocarbon Receptor in Developing Tissues of Two TCDD-Responsive lacZ Mouse Lines
* Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642; Alkermes Inc., Cambridge, Massachusetts 02139
Received July 4, 2005; accepted July 13, 2005
In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can have an immediate impact on developmental processes that then lead to long-term deficits in function. To define the specific tissues affected by TCDD during development, we developed a lacZ-reporter gene mouse model driven by activation of the aryl hydrocarbon receptor (AhR). Exposure to TCDD on gestational day (GD) 14 results in strong activation of the lacZ transgene in numerous tissues including fore and hind paws, ear, and genital tubercle. Experiments were conducted to examine the ability of alternative AhR ligands to activate our model system. The coplanar polychlorinated biphenyl congeners 3,4,5,3',4'-pentachlorobiphenyl (PCB126) and 3,4,3',4'-tetrachlorobiphenyl (PCB77) both induced staining in fetal tissues identical to that observed following TCDD exposure. Exposure of fetuses to the PCB mixture Aroclor 1254 and the non-coplanar congener 2,3,6,2',5'-pentachlorobiphenyl (PCB95) did not result in any activation of the lacZ transgene. In addition to the testing of alternative ligands, another line of reporter mice was generated to determine the potential influence of the site of insertion of the lacZ transgene on the reported observations. Both TCDD and the coplanar PCBs induced a similar pattern of staining in the new line as compared to that observed in the original lacZ reporter mouse line. The ability of AhR ligands, other than TCDD, to activate the AhR-mediated transgene, in combination with the insertion-site independence of the response, strengthens the data previously derived from this model and increases the utility of this system for investigations examining AhR-mediated events during development.
Key Words: aryl hydrocarbon receptor; polychlorinated biphenyls; dioxin; lacZ.
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