title: An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria.
abstract: Mutations in Cu/Zn superoxide dismutase (SOD1) cause a subset of cases of familial amyotrophic lateral sclerosis. Four lines of mice accumulating one of these mutant proteins (G37R) develop severe, progressive motor neuron disease. At lower levels of mutant accumulation, pathology is restricted to lower motor neurons, whereas higher levels cause more severe abnormalities and affect a variety of other neuronal populations. The most obvious cellular abnormality is the presence in axons and dendrites of membrane-bounded vacuoles, which appear to be derived from degenerating mitochondria. Since multiple lines of mice expressing wild-type human SOD1 at similar and higher levels do not show disease, the disease in mice expressing the G37R mutant SOD1 must arise from the acquisition of an adverse property by the mutant enzyme, rather than elevation or loss of SOD1 activity.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Wong
authors.forename: C A
authors.initials: CA
authors.lastname: Pardo
authors.forename: D R
authors.initials: DR
authors.lastname: Borchelt
authors.forename: M K
authors.initials: MK
authors.lastname: Lee
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: S S
authors.initials: SS
authors.lastname: Sisodia
authors.forename: D W
authors.initials: DW
authors.lastname: Cleveland
authors.forename: D L
authors.initials: DL
authors.lastname: Price
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D001369:Axons / Q000473:pathology; D003712:Dendrites / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008928:Mitochondria / Q000473:pathology*; D016472:Motor Neuron Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009046:Motor Neurons / Q000648:ultrastructure; D009154:Mutation; D013482:Superoxide Dismutase / Q000235:genetics*; D014617:Vacuoles / Q000473:pathology*
chemical_list: D013482:Superoxide Dismutase