Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused by expansion of polyglutamine (polyQ) repeat in exon 1 of huntingtin (HTT). In patients, the number of glutamine residues in polyQ tracts are over 35, and it is correlated with age of onset, severity, and disease progression. Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. These pathological aggregates can be transmitted from neuron to another neuron, and this process may explain the pathological spreading of polyQ aggregates. Here, we developed an in vivo model for studying transmission of polyQ aggregates in a highly quantitative manner in real time. HTT exon 1 with expanded polyQ was fused with either N-terminal or C-terminal fragments of Venus fluorescence protein and expressed in pharyngeal muscles and associated neurons, respectively, of C. elegans. Transmission of polyQ proteins was detected using bimolecular fluorescence complementation (BiFC). Mutant polyQ (Q97) was transmitted much more efficiently than wild type polyQ (Q25) and forms numerous inclusion bodies as well. The transmission of Q97 was gradually increased with aging of animal. The animals with polyQ transmission exhibited degenerative phenotypes, such as nerve degeneration, impaired pharyngeal pumping behavior, and reduced life span. The C. elegans model presented here would be a useful in vivo model system for the study of polyQ aggregate propagation and might be applied to the screening of genetic and chemical modifiers of the propagation.

中文翻译：

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秀丽隐杆线虫中聚谷氨酰胺聚集体的细胞间传输。

亨廷顿病（HD）是一种遗传性神经退行性疾病，其特征是亨廷顿（HTT）外显子1的多谷氨酰胺（polyQ）重复扩增引起运动和认知功能障碍。在患者中，polyQ道中的谷氨酰胺残基数量超过35，并且与发病年龄，严重程度和疾病进展相关。polyQ的扩增会增加HTT蛋白聚集的倾向，这一过程已知与神经变性有关。这些病理性聚集体可以从神经元传递到另一个神经元，并且这个过程可以解释polyQ聚集体的病理性扩散。在这里，我们开发了一种体内模型，用于以高度定量的方式实时研究polyQ聚集体的传递。HTT具有扩展的polyQ的外显子1与维纳斯荧光蛋白的N末端或C末端片段融合，并分别在秀丽隐杆线虫的咽肌和相关神经元中表达。使用双分子荧光互补（BiFC）检测了polyQ蛋白的传递。突变体polyQ（Q97）的传递比野生型polyQ（Q25）更有效，并且也形成了许多包涵体。随着动物衰老，Q97的传播逐渐增加。具有polyQ传递的动物表现出变性表型，例如神经变性，咽部抽气行为受损和寿命缩短。在秀丽隐杆线虫模型这里介绍的会是一个有用的体内 模型用于polyQ聚集体繁殖的研究，可用于筛选繁殖的遗传和化学修饰因子。