title: Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment.
abstract: Mutations were identified in the Cu/Zn superoxide dismutase gene (SOD1) in approximately 15% of patients with familial amyotrophic lateral sclerosis. Transgenic animals expressing mutant SOD1 in all tissues develop an ALS-like phenotype. To determine whether neuron-specific expression of mutant SOD1 is sufficient to produce such a phenotype, we generated transgenic animals carrying the G37R mutation that is associated with the familial form of ALS (FALS), which is driven by the neurofilament light chain promoter. The transgenic animals express high levels of the human SOD1 protein in neuronal tissues, especially in the large motor neurons of the spinal cord, but they show no apparent motor deficit at up to 1.5 years of age. Our animal model suggests that neuron-specific expression of ALS-associated mutant human SOD1 may not be sufficient for the development of the disease in mice.
authors.affiliation: Centre for Research in Neuroscience, McGill University, and the Montreal General Hospital Research Institute, Montreal, Quebec, H3G 1A4, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Pramatarova
authors.forename: J
authors.initials: J
authors.lastname: Laganière
authors.forename: J
authors.initials: J
authors.lastname: Roussel
authors.forename: K
authors.initials: K
authors.lastname: Brisebois
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation / Q000235:genetics; D015870:Gene Expression; D005799:Genes, Dominant; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology*; D009154:Mutation; D016900:Neurofilament Proteins / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D000072105:Superoxide Dismutase-1; D019076:Transgenes
chemical_list: D016900:Neurofilament Proteins; C000606290:SOD1 protein, human; C044882:neurofilament protein L; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1