title: Neuromuscular accumulation of mutant superoxide dismutase 1 aggregates in a transgenic mouse model of familial amyotrophic lateral sclerosis.
abstract: Superoxide dismutase 1 (SOD1) aggregates are a histological and biochemical correlate of disease progression in neural tissues from mutant SOD1-linked forms of familial amyotrophic lateral sclerosis (FALS). In the present study, we assayed the monomeric and high molecular weight mutant SOD1 content of nervous, muscle and visceral tissues from transgenic SOD1(G93A) mice using immunoblotting and zymograms. A progressive age-dependent increase in mutant SOD1 level, aggregation and stabilisation by cross-species heterodimers was determined in lumbar spinal cord, sciatic nerve and gastrocnemius muscle. Such biochemical abnormalities were not present in cervical spinal cord, brainstem and diaphragm muscle, nor common to endogenous mouse SOD1. Mutant dismutase activity in general did not increase correspondingly with accumulating protein at later ages. These results suggest that peripheral targets such as hindlimb skeletal muscle and nerve accumulate mutant SOD1 aggregates and may therefore be susceptible to mutant SOD1-mediated toxicity, in addition to lower and upper motor neurons of the central nervous system in transgenic FALS mice.
authors.affiliation: Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Turner
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Lopes
authors.forename: Surindar S
authors.initials: SS
authors.lastname: Cheema
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology*; D009154:Mutation; D009420:Nervous System / Q000201:enzymology*; 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