Neuron-specific expression of mutant superoxide dismutase is sufficient to induce amyotrophic lateral sclerosis in transgenic mice

Dick Jaarsma, Eva Teuling, Elize D Haasdijk, Chris I De Zeeuw, Casper C Hoogenraad

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    172 Citations (Scopus)


    Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), an adult-onset progressive paralytic disease characterized by loss of motor neurons, and cause an ALS-like disease when expressed in mice. Recent data have suggested that motor neuron degeneration results from toxic actions of mutant SOD1 operating in both motor neurons and their neighboring glia, raising the question whether mutant SOD1 expression selectively in neurons is sufficient to induce disease. Here we show that neuronal expression of mutant SOD1 is sufficient to cause motor neuron degeneration and paralysis in transgenic mice with cytosolic dendritic ubiquitinated SOD1 aggregates as the dominant pathological feature. In addition, we show that crossing our neuron-specific mutant SOD1 mice with ubiquitously wild-type SOD1-expressing mice leads to dramatic wild-type SOD1 aggregation in oligodendroglia after the onset of neuronal degeneration. Together, our findings support a pathogenic scenario in which mutant SOD1 in neurons triggers neuronal degeneration, which in turn may facilitate aggregate formation in surrounding glial cells.

    Original languageEnglish
    Pages (from-to)2075-2088
    Number of pages14
    JournalThe Journal of Neuroscience
    Issue number9
    Publication statusPublished - 27-Feb-2008


    • Amyotrophic Lateral Sclerosis
    • Animals
    • Antigens, Thy-1
    • Brain
    • Dendrites
    • Disease Models, Animal
    • Gene Expression Regulation
    • Humans
    • Mice
    • Mice, Transgenic
    • Microscopy, Electron, Transmission
    • Mutation
    • Nerve Tissue Proteins
    • Neurons
    • Oligodendroglia
    • Silver Staining
    • Superoxide Dismutase
    • Ubiquitin
    • alpha-Crystallin B Chain

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