title: Hydrogen-deuterium exchange in vivo to measure turnover of an ALS-associated mutant SOD1 protein in spinal cord of mice.
abstract: Mutations of cytosolic Cu/Zn superoxide dismutase 1 (SOD1) in humans and overexpression of mutant human SOD1 genes in transgenic mice are associated with the motor neuron degenerative condition known as amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease). Gain-of-function toxicity from the mutant protein expressed in motor neurons, associated with its misfolding and aggregation, leads to dysfunction and cell death, associated with paralyzing disease. Here, using hydrogen-deuterium exchange in intact mice in vivo, we have addressed whether an ALS-associated mutant protein, G85R SOD1-YFP, is subject to the same rate of turnover in spinal cord both early in the course of the disease and later. We find that the mutant protein turns over about 10-fold faster than a similarly expressed wild-type fusion and that there is no significant change in the rate of turnover as animals age and disease progresses.
authors.affiliation: Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center, New Haven, Connecticut 06510, USA.
authors.forename: George W
authors.initials: GW
authors.lastname: Farr
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ying
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Fenton
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Horwich
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D041961:Deuterium Exchange Measurement; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D013116:Spinal Cord / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1