The analysis of participation in the ubiquitin proteasome system for understanding the mechanisms of neurodegenerative diseases.

我们通过与带有Vacht-Cre的26S蛋白酶体亚单位Rpt3杂交，建立了运动神经元特异性蛋白酶体缺陷小鼠。表现运动神经元特异性Cre表达的快速小鼠。运动神经元特异性Rpt3缺陷小鼠从8周龄开始出现震颤，从12周龄开始缓慢进行性运动功能障碍。病理结果显示家族性ALS的基因产物如FUS和TDP43表达增加，后者形成胞质包涵体。这些结果表明，运动神经元特异性Rpt3缺陷小鼠代表了散发性ALS的模型。

We have established motor neuron-specific proteasome deficient mice by crossbreeding of flexed mice for Rpt3, a subunit of 26S proteasome with VAChT-Cre. Fast mice that displays motor neuron specific Cre expression. The motor neuron specific Rpt3 deficient mice showed tremor starting from 8 weeks of age and slowly progressive motor dysfunction from 12 weeks of age. Pathological findings revealed increased expression of the gene products of familial ALS such as FUS and TDP43, the latter forming cytoplasmic inclusion bodies. These results suggest that motor neuron-specific Rpt3 deficient mice represent a model for sporadic ALS.