Abstract
Mutations in Alsin are associated with chronic juvenile amyotrophic lateral sclerosis (ALS2), juvenile primary lateral sclerosis and infantile-onset ascending spastic paralysis. The primary pathology and pathogenic mechanism of the disease remain largely unknown. Here we show that alsin-deficient mice have motor impairment and degenerative pathology in the distal corticospinal tracts without apparent motor neuron pathology. Our data suggest that ALS2 is predominantly a distal axonopathy, rather than a neuronopathy in the central nervous system of the mouse model, implying that alsin plays an important role in maintaining the integrity of the corticospinal axons.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amyotrophic Lateral Sclerosis / genetics
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Amyotrophic Lateral Sclerosis / pathology
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Amyotrophic Lateral Sclerosis / physiopathology
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Animals
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Axons / pathology*
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Axons / physiology
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Brain / pathology
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Disease Models, Animal
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Exons
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Female
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Guanine Nucleotide Exchange Factors / deficiency*
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / physiology
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Humans
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Male
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Motor Neurons / pathology
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Motor Neurons / physiology
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Mutation
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Pregnancy
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Spinal Cord / pathology
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
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Superoxide Dismutase-1
Substances
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Als2 protein, mouse
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Guanine Nucleotide Exchange Factors
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SOD1 protein, human
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Sod1 protein, mouse
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Superoxide Dismutase
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Superoxide Dismutase-1