title: Novel mutations in an otherwise strictly conserved domain of CuZn superoxide dismutase.
abstract: All mutations in the human gene for CuZn superoxide dismutase (CuZnSOD) reported to date are associated with the disease amyotrophic lateral sclerosis (ALS). These mutations, mostly of a familial nature (ALS 1, MIM 105400), span all of the coding region of this enzyme except for a highly conserved centrally located domain that includes all of exon III. We describe the identification and characterization of two mutations in this region, both found in mice. One mutation, a glutamate to lysine amino acid substitution was found in position 77 (E77K) of the strain SOD1/Ei distributed by the Jackson Laboratory. The other mutation, a lysine to glutamate substitution at position 70 (K70E) of a human transgene, was discovered in mouse line TgHS/SF-155. Enzyme activity measurements and heterodimer analysis of the CuZn SOD variant in SOD1/Ei suggest a mild loss of activity, which differs from the enzyme activity losses detected in patients with autosomal dominant ALS 1. Similarly, the presence of the mutant transgene in TgHS/SF 155 does not produce any phenotypic manifestations.
authors.affiliation: Department of Pediatrics, University of California, San Francisco 94143-0748, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Luche
authors.forename: R
authors.initials: R
authors.lastname: Maiwald
authors.forename: E J
authors.initials: EJ
authors.lastname: Carlson
authors.forename: C J
authors.initials: CJ
authors.lastname: Epstein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics*
chemical_list: D013482:Superoxide Dismutase