Expression of human FUS protein in Drosophila leads to progressive neurodegeneration.
10.1007/s13238-011-1065-7
- Author:
Yanbo CHEN
1
;
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
Author Information
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, China.
- Publication Type:Journal Article
- MeSH:
Aged;
Aging;
genetics;
metabolism;
pathology;
Amyotrophic Lateral Sclerosis;
genetics;
metabolism;
pathology;
Animals;
Animals, Genetically Modified;
Disease Models, Animal;
Drosophila melanogaster;
genetics;
metabolism;
Gene Expression;
Humans;
Microscopy, Electron, Scanning;
Motor Neurons;
metabolism;
pathology;
Mushroom Bodies;
metabolism;
pathology;
Mutant Proteins;
genetics;
metabolism;
Mutation;
Photoreceptor Cells, Invertebrate;
metabolism;
pathology;
Plasmids;
RNA-Binding Protein FUS;
genetics;
metabolism;
Recombinant Fusion Proteins;
genetics;
metabolism;
Retinal Degeneration;
pathology;
physiopathology;
Transfection
- From:
Protein & Cell
2011;2(6):477-486
- CountryChina
- Language:English
-
Abstract:
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.
