PUBLICATION

Mutant Human FUS Is Ubiquitously Mislocalized and Generates Persistent Stress Granules in Primary Cultured Transgenic Zebrafish Cells

Authors
Acosta, J.R., Goldsbury, C., Winnick, C., Badrock, A.P., Fraser, S.T., Laird, A.S., Hall, T.E., Don, E.K., Fifita, J.A., Blair, I.P., Nicholson, G.A., Cole, N.J.
ID
ZDB-PUB-140610-2
Date
2014
Source
PLoS One   9(6): e90572 (Journal)
Registered Authors
Badrock, Andrew P., Cole, Nicholas, Don, Emily, Hall, Thomas
Keywords
none
MeSH Terms
  • Cells, Cultured
  • Cytoplasmic Granules/metabolism*
  • Humans
  • Mutation*
  • Motor Neurons/cytology
  • Cytosol/metabolism*
  • Zebrafish/genetics*
  • Zebrafish/metabolism*
  • Animals, Genetically Modified
  • Animals
  • Protein Transport/genetics
  • RNA-Binding Protein FUS/genetics*
  • RNA-Binding Protein FUS/metabolism*
(all 13)
PubMed
24912067 Full text @ PLoS One
Abstract
FUS mutations can occur in familial amyotrophic lateral sclerosis (fALS), a neurodegenerative disease with cytoplasmic FUS inclusion bodies in motor neurons. To investigate FUS pathology, we generated transgenic zebrafish expressing GFP-tagged wild-type or fALS (R521C) human FUS. Cell cultures were made from these zebrafish and the subcellular localization of human FUS and the generation of stress granule (SG) inclusions examined in different cell types, including differentiated motor neurons. We demonstrate that mutant FUS is mislocalized from the nucleus to the cytosol to a similar extent in motor neurons and all other cell types. Both wild-type and R521C FUS localized to SGs in zebrafish cells, demonstrating an intrinsic ability of human FUS to accumulate in SGs irrespective of the presence of disease-associated mutations or specific cell type. However, elevation in relative cytosolic to nuclear FUS by the R521C mutation led to a significant increase in SG assembly and persistence within a sub population of vulnerable cells, although these cells were not selectively motor neurons.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mq1TgTransgenic Insertion
    mq2TgTransgenic Insertion
      mq3TgTransgenic Insertion
        mq4TgTransgenic Insertion
          mq7TgTransgenic Insertion
            rw0TgTransgenic Insertion
              s1020tEtTransgenic Insertion
                s1984tTgTransgenic Insertion
                  1 - 8 of 8
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                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  No data available
                  Fish
                  Antibodies
                  Name Type Antigen Genes Isotypes Host Organism
                  Ab1-eif3epolyclonal
                    IgGRabbit
                    Ab2-fuspolyclonal
                      IgGRabbit
                      Ab2-islmonoclonalIgG2bMouse
                      Ab-3A10monoclonal
                        IgG1Mouse
                        zn-8monoclonalIgG1Mouse
                        zn-12monoclonal
                          IgG1Mouse
                          1 - 6 of 6
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                          Orthology
                          No data available
                          Engineered Foreign Genes
                          Marker Marker Type Name
                          EGFPEFGEGFP
                          GAL4EFGGAL4
                          GFPEFGGFP
                          mCherryEFGmCherry
                          mKOFP2EFGmKOFP2
                          1 - 5 of 5
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                          Mapping
                          No data available