A transgenic mouse model of the ubiquitin/proteasome system
A transgenic mouse model of the ubiquitin/proteasome system
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DOI：
10.1038/nbt851
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发表时间：
2003-08-01
影响因子：
46.9
通讯作者：
Dantuma, NP
中科院分区：
文献类型：
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作者：
Lindsten, K;Menéndez-Benito, V;Dantuma, NP
泛素/蛋白酶体系统的损伤被认为在阿尔茨海默病和帕金森病等神经退行性疾病中发挥作用。虽然最近的研究证实，一些疾病相关的蛋白可以阻止蛋白酶体的降解，而且尽管存在这两种疾病的优秀动物模型，但缺乏关于该系统的体内数据。我们开发了一个用于体内分析泛素/蛋白酶体系统的模型，方法是产生携带结构性活性降解信号的绿色荧光蛋白(GFP)报告基因的小鼠品系。对转基因动物给予蛋白酶体抑制剂后，GFP在多个组织中大量积累，证实了该报告的体内功能。此外，在阿尔茨海默病中发现的一种异常泛素UBB+1诱导了报告基因在初级神经元中的积累。这些转基因动物为在生理或病理条件下监测泛素/蛋白酶体系统的状态提供了一种工具。
Impairment of the ubiquitin/proteasome system has been proposed to play a role in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Although recent studies confirmed that some disease-related proteins block proteasomal degradation, and despite the existence of excellent animal models of both diseases, in vivo data about the system are lacking. We have developed a model for in vivo analysis of the ubiquitin/proteasome system by generating mouse strains transgenic for a green fluorescent protein (GFP) reporter carrying a constitutively active degradation signal. Administration of proteasome inhibitors to the transgenic animals resulted in a substantial accumulation of GFP in multiple tissues, confirming the in vivo functionality of the reporter. Moreover, accumulation of the reporter was induced in primary neurons by UBB+1, an aberrant ubiquitin found in Alzheimer disease. These transgenic animals provide a tool for monitoring the status of the ubiquitin/proteasome system in physiologic or pathologic conditions.