鼠类Ah受体信号传导的遗传模型。

IF 3.4 2区 医学 Q2 PHARMACOLOGY & PHARMACY Drug Metabolism Reviews Pub Date : 2021-08-01 Epub Date: 2021-08-25 DOI:10.1080/03602532.2021.1955916
Rachel H Wilson, Christopher A Bradfield
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引用次数: 7

摘要

芳烃受体(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。这种受体多年来一直是毒理学领域感兴趣的分子,因为它最初被发现介导某些环境污染物的毒性作用,如苯并(a)芘和2,3,7,8-四氯二苯并-对二恶英。虽然所有的动物都表达这种蛋白,但在受体大小和对配体的反应方面自然存在差异。这种自然发生的变异,特别是在小鼠中,已经成为发现和早期表征AHR的重要工具。包括同源小鼠和Ahr位点诱导突变在内的遗传模型已被证明对进一步了解Ahr在适应性代谢和tcdd诱导毒性中的作用是非常宝贵的。Ahr缺失小鼠的创建和检测揭示了Ahr在血管和肝脏发育以及免疫系统介导中的重要生理作用。在这篇综述中,我们试图对迄今为止有助于理解AHR生物学的许多AHR模型进行概述。我们描述了自然发生的多态性、同源模型、小鼠Ah受体Ahr位点和结合伙伴Ah受体核转运子和伴侣Ah受体相关的9个位点的诱导突变,并简要描述了大鼠Ah受体自然发生和诱导突变。
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Rodent genetic models of Ah receptor signaling.

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(a)pyrene and 2,3,7,8-tetrachlorodibenzo-p-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 Ahr locus have proven invaluable in further understanding the role of the AHR in adaptive metabolism and TCDD-induced toxicity. The creation and examination of Ahr 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 Ahr 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.

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来源期刊
Drug Metabolism Reviews
Drug Metabolism Reviews 医学-药学
CiteScore
11.10
自引率
1.70%
发文量
21
审稿时长
1 months
期刊介绍: Drug Metabolism Reviews consistently provides critically needed reviews of an impressive array of drug metabolism research-covering established, new, and potential drugs; environmentally toxic chemicals; absorption; metabolism and excretion; and enzymology of all living species. Additionally, the journal offers new hypotheses of interest to diverse groups of medical professionals including pharmacologists, toxicologists, chemists, microbiologists, pharmacokineticists, immunologists, mass spectroscopists, as well as enzymologists working in xenobiotic biotransformation.
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