title: Distal axonopathy in an alsin-deficient mouse model.
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.
authors.affiliation: Department of Neurology and Clinical Neurosciences, Northwestern University Institute for Neuroscience, Chicago, IL 60611, USA. h-deng@northwestern.edu
authors.forename: Han-Xiang
authors.initials: HX
authors.lastname: Deng
authors.forename: Hong
authors.initials: H
authors.lastname: Zhai
authors.forename: Ronggen
authors.initials: R
authors.lastname: Fu
authors.forename: Yong
authors.initials: Y
authors.lastname: Shi
authors.forename: George H
authors.initials: GH
authors.lastname: Gorrie
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Erdong
authors.initials: E
authors.lastname: Liu
authors.forename: Mauro C
authors.initials: MC
authors.lastname: Dal Canto
authors.forename: Enrico
authors.initials: E
authors.lastname: Mugnaini
authors.forename: Teepu
authors.initials: T
authors.lastname: Siddique
mesh_terms: D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D005091:Exons; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D009154:Mutation; D011247:Pregnancy; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: C512358:Als2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1