Expression of human FUS protein in Drosophila leads to progressive neurodegeneration  

作　　者：Yanbo Chen Mengxue Yang Jianwen Deng Xiaoping Chen Ye Ye Li Zhu Jianghong Liu Haihong Ye Yan Shen Yan Li Elizabeth J.Rao Kazuo Fushimi Xiaohong Zhou Eileen H.Bigio Marsel Mesulam Qi Xu Jane Y.Wu 

机构地区：[1]National Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Science and Peking Union Medical College,Tsinghua University,Beijing 100730,China [2]State Key Laboratory of Brain and Cognitive Science,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [3]Department of Neurology,Center for Genetic Medicine,Lurie Cancer Center,Northwestern University Feinberg School of Medicine,303 E.Superior St.,Chicago,IL 60611 USA [4]The Cognitive Neurology&Alzheimer's Disease Center,Northwestern University Feinberg School of Medicine,303 E.Chicago Ave.,Chicago,IL 60611,USA [5]Trumbull College,Yale University,New Haven,CT 06511,USA

出　　处：《Protein & Cell》2011年第6期477-486,共10页蛋白质与细胞（英文版）

基　　金：supported by the National Basic Research Program(973 Program)(Grant No.2009CB825402);supported by the National Basic Research Program(973 Program)(Grant No.2010CB529603).

摘　　要：Mutations in the Fused in sarcoma/Translated in liposarcoma gene(FUS/TLS,FUS)have been identified among patients with amyotrophic lateral sclerosis(ALS).FUS protein aggregation is a major pathological hallmark of FUS proteinopathy,a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies.We prepared transgenic Drosophila expressing either the wild type(Wt)or ALS-mutant human FUS protein(hFUS)using the UAS-Gal4 system.When expressing Wt,R524S or P525L mutant FUS in photoreceptors,mushroom bodies(MBs)or motor neurons(MNs),transgenic flies show age-dependent progressive neural damages,including axonal loss in MB neurons,morphological changes and functional impairment in MNs.The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy,representing the first stable animal model for this group of devastating diseases.

关 键 词：frontotemporal lobar degeneration(FTLD) FUS proteinopathy animal model amyotrophic lateral sclerosis NEURODEGENERATION 

分 类 号：R44[医药卫生—诊断学]