Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, WI, USA.
Department of Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Drug Metab Rev. 2021 Aug;53(3):350-374. doi: 10.1080/03602532.2021.1955916. Epub 2021 Aug 25.
The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that is a member of the PER-ARNT-SIM superfamily of environmental sensors. This receptor has been a molecule of interest for many years in the field of toxicology, as it was originally discovered to mediate the toxic effects of certain environmental pollutants like benzo()pyrene and 2,3,7,8-tetrachlorodibenzo--dioxin. While all animals express this protein, there is naturally occurring variability in receptor size and responsiveness to ligand. This naturally occurring variation, particularly in mice, has been an essential tool in the discovery and early characterization of the AHR. Genetic models including congenic mice and induced mutations at the locus have proven invaluable in further understanding the role of the AHR in adaptive metabolism and TCDD-induced toxicity. The creation and examination of null mice revealed an important physiological role for the AHR in vascular and hepatic development and mediation of the immune system. In this review, we attempt to provide an overview to many of the AHR models that have aided in the understanding of AHR biology thus far. We describe the naturally occurring polymorphisms, congenic models, induced mutations at the locus and at the binding partner Ah Receptor Nuclear Translocator and chaperone, Ah receptor associated 9 loci in mice, with a brief description of naturally occurring and induced mutations in rats.
芳香烃受体 (AHR) 是一种配体激活的转录因子,是环境传感器 PER-ARNT-SIM 超家族的成员。该受体多年来一直是毒理学领域的研究对象,因为它最初被发现可介导某些环境污染物(如苯并()芘和 2,3,7,8-四氯二苯并对二恶英)的毒性作用。虽然所有动物都表达这种蛋白质,但受体的大小和对配体的反应性存在天然变异性。这种天然变异,特别是在小鼠中,一直是发现和早期表征 AHR 的重要工具。包括近交系小鼠和 基因座诱导突变在内的遗传模型已被证明在进一步理解 AHR 在适应性代谢和 TCDD 诱导毒性中的作用方面非常宝贵。 基因缺失小鼠的创建和检查揭示了 AHR 在血管和肝脏发育以及免疫系统调节中的重要生理作用。在这篇综述中,我们试图提供迄今为止帮助理解 AHR 生物学的许多 AHR 模型的概述。我们描述了小鼠中存在的多态性、近交系模型、 基因座诱导突变以及结合伴侣 Ah 受体核转位因子和伴侣蛋白 Ah 受体相关 9 基因座,简要描述了大鼠中存在的和诱导突变。