Protein & Cell

, Volume 2, Issue 6, pp 477–486

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
Research Article

DOI: 10.1007/s13238-011-1065-7

Cite this article as:
Chen, Y., Yang, M., Deng, J. et al. Protein Cell (2011) 2: 477. doi:10.1007/s13238-011-1065-7

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.

Keywords

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

Supplementary material

13238_2011_1065_MOESM1_ESM.pdf (448 kb)
Supplementary material, approximately 447 KB.

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Yanbo Chen
    • 1
    • 3
  • Mengxue Yang
    • 2
  • Jianwen Deng
    • 2
  • Xiaoping Chen
    • 3
  • Ye Ye
    • 2
  • Li Zhu
    • 2
  • Jianghong Liu
    • 2
  • Haihong Ye
    • 2
  • Yan Shen
    • 1
  • Yan Li
    • 2
    • 3
  • Elizabeth J. Rao
    • 3
    • 5
  • Kazuo Fushimi
    • 3
  • Xiaohong Zhou
    • 3
  • Eileen H. Bigio
    • 4
  • Marsel Mesulam
    • 4
  • Qi Xu
    • 1
  • Jane Y. Wu
    • 2
    • 3
  1. 1.National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Science and Peking Union Medical CollegeTsinghua UniversityBeijingChina
  2. 2.State Key Laboratory of Brain and Cognitive Science, Institute of BiophysicsChinese Academy of SciencesBeijingChina
  3. 3.Department of Neurology, Center for Genetic Medicine, Lurie Cancer CenterNorthwestern University Feinberg School of MedicineChicagoUSA
  4. 4.The Cognitive Neurology & Alzheimer’s Disease CenterNorthwestern University Feinberg School of MedicineChicagoUSA
  5. 5.Trumbull CollegeYale UniversityNew HavenUSA