title: Neuronal-specific expression of human copper-zinc superoxide dismutase gene in transgenic mice: animal model of gene dosage effects in Down's syndrome.
abstract: It has been suggested that copper-zinc superoxide dismutase (CuZn SOD) increment, by accelerating hydrogen peroxide formation, might promote oxidative damage within trisomy 21 cells and might be involved in the various neurobiological abnormalities found in Down's syndrome such as premature aging and Alzheimer-type neurological lesions. In order to test this hypothesis, we have developed strains of transgenic mice carrying the human CuZn SOD gene. The human transgene expression resulted in increased CuZn SOD activity predominantly in the brain (1.93 fold). Immunohistochemical and in situ hybridization analysis of brain sections revealed that human CuZn SOD protein and mRNA was preferentially expressed in neurons, particularly in pyramidal cells of Ammon's horn and granule cells of gyrus dentate. The amount of thiobarbituric acid (TBA)-reactive material was significantly higher in transgenic brains compared to controls, strongly suggesting an increased level of peroxidation in vivo. These results support the notion that CuZn SOD gene dosage effect could play a role in the pathogenesis of rapid aging features in the brain of Down's syndrome patients.
authors.affiliation: URA CNRS 1335, Laboratoire de Biochemie Génétique, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Ceballos-Picot
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: A
authors.initials: A
authors.lastname: Defossez
authors.forename: F
authors.initials: F
authors.lastname: Javoy-Agid
authors.forename: M
authors.initials: M
authors.lastname: Lafon
authors.forename: J L
authors.initials: JL
authors.lastname: Blouin
authors.forename: P M
authors.initials: PM
authors.lastname: Sinet
mesh_terms: D000375:Aging; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D001921:Brain / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008099:Liver / Q000254:growth & development / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000201:enzymology*; D009928:Organ Specificity; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D012313:RNA; D004247:DNA; D013482:Superoxide Dismutase