Title: Overexpression of mutant superoxide dismutase 1 causes a motor axonopathy in the zebrafish
Authors: Lemmens, Robin ×
Van Hoecke, Annelies
Hersmus, Nicole
Geelen, Veerle
D'Hollander, Isabelle
Thijs, Vincent
Van Den Bosch, Ludo
Carmeliet, Peter
Robberecht, Wim #
Issue Date: Oct-2007
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:16 issue:19 pages:2359-2365
Abstract: The development of small animal models is of major interest to unravel the pathogenesis and treatment of neurodegenerative diseases, especially because of their potential in large-scale chemical and genetic screening. We have investigated the zebrafish as a model to study amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder characterized by the selective loss of motor neurons, caused by mutations in superoxide dismutase 1 (SOD1) in a subset of patients. Overexpression of mutant human SOD1 in zebrafish embryos induced a motor axonopathy that was specific, dose-dependent and found for all mutations studied. Moreover, using this newly established animal model for ALS we investigated the role of a known modifier in the disease: vascular endothelial growth factor (VEGF). Lowering VEGF induced a more severe phenotype while upregulating VEGF rescued the mutant SOD1 axonopathy. This novel zebrafish model underscores the potential of VEGF for the treatment of ALS and furthermore will permit large scale genetic and chemical screening to facilitate the identification of new therapeutic targets in motor neuron disease.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Molecular and Vascular Biology
Laboratory for Neurobiology (Vesalius Research Center)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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