title: Expression of human Cu-Zn superoxide dismutase gene in transgenic mice: model for gene dosage effect in Down syndrome.
abstract: It was suggested that increased Cu-Zn superoxide dismutase (SOD-1) might be involved in the various biological abnormalities found in Down's syndrome (DS) such as premature aging and Alzheimer-type neurological lesions. As a model system for testing this hypothesis we have developed two strains of transgenic mice carrying only one copy of the human SOD-1 gene. In the first strain (TG1), no expression has been found by northern blot analysis. The second strain (TG2) exhibited human SOD-1 mRNA and increased SOD-1 activity in the brain (1.93 fold), in the heart (1.69 fold), thymus (1.49 fold) and to a lesser extent in muscle (1.25 fold), liver (1.19 fold), kidney (1.18 fold), spleen (1.35 fold), lung (1.26 fold) and erythrocytes (1.09 fold). In this strain, increased SOD-1 activity in the brain did not induce modifications in the seleno-dependent glutathione peroxidase, glutathione reductase and glutathione S-transferase activities. In brain homogenates, we have focused our studies on Tau proteins which are known to be the major antigenic components of paired helical filaments (PHF), both in DS and Alzheimer's disease. Our results suggested that, in our experimental conditions, the overexpression of SOD-1 did not induce the modifications of Tau proteins similar to those seen during neurofibrillary degeneration.
authors.affiliation: URA CNRS 1335, Laboratoire de Biochimie génétique, Hôpital Necker, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Ceballos
authors.forename: A
authors.initials: A
authors.lastname: Nicole
authors.forename: P
authors.initials: P
authors.lastname: Briand
authors.forename: G
authors.initials: G
authors.lastname: Grimber
authors.forename: A
authors.initials: A
authors.lastname: Delacourte
authors.forename: S
authors.initials: S
authors.lastname: Flament
authors.forename: J L
authors.initials: JL
authors.lastname: Blouin
authors.forename: M
authors.initials: M
authors.lastname: Thevenin
authors.forename: P
authors.initials: P
authors.lastname: Kamoun
authors.forename: P M
authors.initials: PM
authors.lastname: Sinet
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D003300:Copper / Q000737:chemistry; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics*; D005609:Free Radicals; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000032:analysis; D010100:Oxygen / Q000737:chemistry; D013482:Superoxide Dismutase / Q000235:genetics*; D015032:Zinc / Q000737:chemistry; D016875:tau Proteins
chemical_list: D005609:Free Radicals; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D016875:tau Proteins; D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc; D010100:Oxygen