The constitutively active Ah receptor (CA-AhR) mouse as a potential model for dioxin exposure - Effects in vital organs
The constitutively active Ah receptor (CA-AhR) mouse as a potential model for dioxin exposure - Effects in vital organs
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DOI：
10.1016/j.tox.2006.04.045
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发表时间：
2006-07-25
期刊：
影响因子：
4.5
通讯作者：
Hanberg, Annika
中科院分区：
文献类型：
--
作者：
Brunnberg, Sara;Andersson, Patrik;Hanberg, Annika
二恶英/芳烃受体（AhR）介导大多数（如果不是全部）二恶英的毒性作用，并作为配体激活的转录因子调节一系列基因的转录。为了研究Ah受体配体毒性背后的机制，我们建立了表达组成型活性Ah受体（CA-AhR）的转基因小鼠模型。突变型Ah受体在研究的所有器官中表达并具有功能活性。本研究的目的是表征组织病理学，CA-AhR的表型方面的肝脏，肾脏，肺，心脏，脾脏和胸腺的雄性和雌性转基因CA-AhR小鼠。此外，还使用AhR靶基因CYP 1A 1的上调作为标志物来检查CA-AhR的细胞特异性活性。肝脏、肾脏和心脏的相对重量增加，而胸腺的相对重量减少。此外，观察到肝脏、肾脏和脾脏的轻微形态学病变。CYP 1A 1的表达被发现在对应于内皮细胞在所有的器官研究的细胞。在某些组织中，其他细胞类型，如肝细胞、肾小管细胞和Clara细胞表达CYP 1A 1。CA-AhR小鼠中对器官重量的影响和CYP 1A 1的细胞表达与TCDD暴露小鼠中的观察结果一致。总之，这一特征进一步支持CA-AhR小鼠是AhR终身持续低水平活动的有用模型，即一般人群中人类的二恶英暴露情况。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
The dioxin/aryl hydrocarbon receptor (AhR) mediates most, if not all, toxic effects of dioxins and functions as a ligand-activated transcription factor regulating transcription of a battery of genes. In order to study the mechanisms behind the toxicity of ligands of the Ah receptor we have created a transgenic mouse model expressing a constitutively active Ah receptor (CA-AhR). The mutant Ah receptor is expressed and functionally active in all organs studied. The purpose of the present study was to characterize histopathologically, the phenotype of the CA-AhR with regard to the liver, kidney, lung, heart, spleen and thymus of male and female transgenic CA-AhR mice. Moreover, cell-specific activity of the CA-AhR using up-regulation of the AhR target gene CYP1A1 as a marker, was also examined. The relative weight of liver, kidney and heart were increased while relative thymus weight was decreased. Furthermore, slight morphological lesions of the liver, kidney and spleen was seen. Expression of CYP1A1 was found in cells corresponding to endothelial cells in all of the organs studied. In some tissues additional cell types, such as hepatocytes, renal tubuli cell and Clara cells expressed CYP1A1 Both the effects on organ weights and the cellular expression of CYP1A1 in CA-AhR mice correspond well to observations in TCDD-exposed mice. In conclusion, this characterization further support that the CA-AhR mouse is a useful model for life-long continuous low-level activity of the AhR, i.e. the dioxin exposure situation of humans of the general population. (c) 2006 Elsevier Ireland Ltd. All rights reserved.