Expression of human FUS protein in Drosophila leads to progressive neurodegeneration

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)477-486
Number of pages10
JournalProtein and Cell
Volume2
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • FUS proteinopathy
  • amyotrophic lateral sclerosis
  • animal model
  • frontotemporal lobar degeneration (FTLD)
  • neurodegeneration

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Drug Discovery
  • Cell Biology

Fingerprint

Dive into the research topics of 'Expression of human FUS protein in Drosophila leads to progressive neurodegeneration'. Together they form a unique fingerprint.

Cite this