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Protein Cell. 2011 June; 2(6): 477–486.
Published online 2011 July 12. doi:  10.1007/s13238-011-1065-7
PMCID: PMC3563268
NIHMSID: NIHMS379993

Expression of human FUS protein in Drosophila leads to progressive neurodegeneration

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.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-011-1065-7 and is accessible for authorized users.

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

Electronic supplementary material

Footnotes

These authors contributed equally to the work.

Contributor Information

Qi Xu, moc.liamg@alegnauxiq.

Jane Y. Wu, ude.nretsewhtron@uw-enaj.

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