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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aging / genetics
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Aging / metabolism*
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Aging / pathology
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Amyotrophic Lateral Sclerosis* / genetics
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Amyotrophic Lateral Sclerosis* / metabolism
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Amyotrophic Lateral Sclerosis* / pathology
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Animals
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Animals, Genetically Modified
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Disease Models, Animal
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Drosophila melanogaster* / genetics
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Drosophila melanogaster* / metabolism
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Gene Expression
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Humans
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Microscopy, Electron, Scanning
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Motor Neurons / metabolism
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Motor Neurons / pathology*
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Mushroom Bodies / metabolism
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Mushroom Bodies / pathology*
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Mutant Proteins* / genetics
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Mutant Proteins* / metabolism
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Mutation
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Photoreceptor Cells, Invertebrate / metabolism
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Photoreceptor Cells, Invertebrate / pathology*
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Plasmids
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RNA-Binding Protein FUS* / genetics
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RNA-Binding Protein FUS* / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Retinal Degeneration / pathology
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Retinal Degeneration / physiopathology
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Transfection
Substances
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Mutant Proteins
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RNA-Binding Protein FUS
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Recombinant Fusion Proteins