title: Mice Overexpressing Both Non-Mutated Human SOD1 and Mutated SOD1(G93A) Genes: A Competent Experimental Model for Studying Iron Metabolism in Amyotrophic Lateral Sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration and loss of motor neurons in the spinal cord, brainstem and motor cortex. Up to 10% of ALS cases are inherited (familial, fALS) and associated with mutations, frequently in the superoxide dismutase 1 (SOD1) gene. Rodent transgenic models of ALS are often used to elucidate a complex pathogenesis of this disease. Of importance, both ALS patients and animals carrying mutated human SOD1 gene show symptoms of oxidative stress and iron metabolism misregulation. The aim of our study was to characterize changes in iron metabolism in one of the most commonly used models of ALS - transgenic mice overexpressing human mutated SOD1(G93A) gene. We analyzed the expression of iron-related genes in asymptomatic, 2-month-old and symptomatic, 4-month-old SOD1(G93A) mice. In parallel, respective age-matched mice overexpressing human non-mutated SOD1 transgene and control mice were analyzed. We demonstrate that the overexpression of both SOD1 and SOD1(G93A) genes account for a substantial increase in SOD1 protein levels and activity in selected tissues and that not all the changes in iron metabolism genes expression are specific for the overexpression of the mutated form of SOD1.
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences Magdalenka, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gajowiak
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences Magdalenka, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Styś
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences Magdalenka, Poland.
authors.forename: Rafał R
authors.initials: RR
authors.lastname: Starzyński
authors.affiliation: Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University Kraków, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bednarz
authors.affiliation: Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lenartowicz
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences Magdalenka, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Staroń
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences Magdalenka, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Lipiński
keywords: ALS; G93A; SOD1; heme oxygenase 1; iron; neurons; oxidative stress; skeletal muscle