Expression of human FUS protein in Drosophila leads to progressive neurodegeneration

被引：82

作者：

Chen, Yanbo ^{[1
,2
,4
]}

Yang, Mengxue ^{[3
]}

Deng, Jianwen ^{[3
]}

Chen, Xiaoping ^{[4
]}

Ye, Ye ^{[3
]}

Zhu, Li ^{[3
]}

Liu, Jianghong ^{[3
]}

Ye, Haihong ^{[3
]}

Shen, Yan ^{[1
,2
]}

Li, Yan ^{[3
,4
]}

Rao, Elizabeth J. ^{[4
,6
]}

Fushimi, Kazuo ^{[4
]}

Zhou, Xiaohong ^{[4
]}

Bigio, Eileen H. ^{[5
]}

Mesulam, Marsel ^{[5
]}

Xu, Qi ^{[1
,2
]}

Wu, Jane Y. ^{[3
,4
]}

机构：

[1] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China

[2] Tsinghua Univ, Peking Union Med Coll, Beijing 100730, Peoples R China

[3] Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China

[4] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Ctr Genet Med,Lurie Canc Ctr, Chicago, IL 60611 USA

[5] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA

[6] Yale Univ, Trumbull Coll, New Haven, CT 06511 USA

来源：

PROTEIN & CELL | 2011年 / 2卷 / 06期

关键词：

frontotemporal lobar degeneration (FTLD); FUS proteinopathy; animal model; amyotrophic lateral sclerosis; neurodegeneration; AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; RNA-BINDING PROTEIN; BASOPHILIC INCLUSIONS; MUTATIONS; TLS; ACTIVATION; MORPHOLOGY; TDP-43; MODEL;

D O I：

10.1007/s13238-011-1065-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

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.

引用

页码：477 / 486

页数：10

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