Coplanar Polychlorinated Biphenyls Activate the Aryl Hydrocarbon Receptor in Developing Tissues of Two TCDD-Responsive lacZ Mouse Lines
Open Access
- 20 July 2005
- journal article
- research article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 87 (2), 529-536
- https://doi.org/10.1093/toxsci/kfi260
Abstract
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.Keywords
This publication has 23 references indexed in Scilit:
- Retionic Acid and Its Receptors Are Required for Expression of Aryl Hydrocarbon Receptor mRNA and Embryonic Development of Blood Vessel and Bone in the Medaka Fish, Oryzias latipesZoological Science, 2004
- Non-coplanar 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) Amplifies Ionotropic Glutamate Receptor Signaling in Embryonic Cerebellar Granule Neurons by a Mechanism Involving Ryanodine ReceptorsToxicological Sciences, 2003
- Relative Contributions of Affinity and Intrinsic Efficacy to Aryl Hydrocarbon Receptor Ligand PotencyToxicology and Applied Pharmacology, 2000
- Gestational and lactational exposure to TCDD or coplanar PCBs alters adult expression of saccharin preference behavior in female ratsNeurotoxicology and Teratology, 2000
- Behavioral and electrophysiological estimates of visual thresholds in awake rats treated with 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126)Neurotoxicology and Teratology, 2000
- Hearing loss following exposure during development to polychlorinated biphenyls: A cochlear site of actionHearing Research, 2000
- Non-carcinogenic effects of TCDD in animalsFood Additives & Contaminants, 2000
- Low-Frequency Hearing Loss Following Perinatal Exposure to 3,3′,4,4′,5-Pentachlorobiphenyl (PCB 126) in RatsNeurotoxicology and Teratology, 1999
- The Aryl Hydrocarbon Receptor ComplexAnnual Review of Pharmacology and Toxicology, 1995
- Separable Regulatory Elements Governing myogenin Transcription in Mouse EmbryogenesisScience, 1993