A transgenic mouse model for monitoring endoplasmic reticulum stress
A transgenic mouse model for monitoring endoplasmic reticulum stress
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DOI：
10.1038/nm970
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发表时间：
2004-01-01
期刊：
影响因子：
82.9
通讯作者：
Miura, M
中科院分区：
文献类型：
--
作者：
Iwawaki, T;Akai, R;Miura, M
内质网（ER）应激是由未折叠蛋白在内质网腔内的积累引起的，并且与血管和神经退行性疾病相关。虽然已经使用这些疾病的动物模型研究了ER应激和一些疾病相关蛋白之间的联系，但没有关于ER应激的体内数据。在这里，我们报告了一种新的方法来监测ER应力在体内，基于XBP-1 mRNA剪接肌醇需要-1（IRE-1）在ER应力。通过融合XBP-1和venus（绿色荧光蛋白的变体）构建应激指示剂。在应激期间，剪接的指示mRNA被翻译成XBP-1-venus融合蛋白，其可以通过其荧光检测。我们使用转基因动物表达ER应激指标，以表明它可以用于监测生理和病理ER应激在体内。
Endoplasmic reticulum (ER) stress is caused by the accumulation of unfolded proteins in the ER lumen, and is associated with vascular and neurodegenerative diseases. Although the connection between ER stress and some disease-related proteins has been studied using animal models of these diseases, no in vivo data concerning ER stress are available. Here we report a new method for monitoring ER stress in vivo, based on XBP-1 mRNA splicing by inositol requiring-1 (IRE-1) during ER stress. The stress indicator was constructed by fusing XBP-1 and venus, a variant of green fluorescent protein. During stress, the spliced indicator mRNA is translated into an XBP-1-venus fusion protein, which can be detected by its fluorescence. We used transgenic animals expressing the ER stress indicator to show that it can be used to monitor physiological and pathological ER stress in vivo.