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
Supplementary material, approximately 447 KB.
Footnotes
These authors contributed equally to the work.
Electronic Supplementary Material
Supplementary material is available for this article at 10.1007/s13238-011-1065-7 and is accessible for authorized users.
Contributor Information
Qi Xu, Email: qixuangela@gmail.com.
Jane Y. Wu, Email: jane-wu@northwestern.edu
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