AUTHOR=Gajowiak Anna , Styś Agnieszka , Starzyński Rafał R. , Bednarz Aleksandra , Lenartowicz Małgorzata , Staroń Robert , Lipiński Paweł 

TITLE=Mice Overexpressing Both Non-Mutated Human SOD1 and Mutated SOD1G93A Genes: A Competent Experimental Model for Studying Iron Metabolism in Amyotrophic Lateral Sclerosis

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=8

YEAR=2016

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2015.00082

DOI=10.3389/fnmol.2015.00082

ISSN=1662-5099

ABSTRACT=<p>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 (<italic>SOD1</italic>) 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 <italic>SOD1</italic> 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 <italic>SOD1<sup>G93A</sup></italic> gene. We analyzed the expression of iron-related genes in asymptomatic, 2-month-old and symptomatic, 4-month-old <italic>SOD1<sup>G93A</sup></italic> mice. In parallel, respective age-matched mice overexpressing human non-mutated <italic>SOD1</italic> transgene and control mice were analyzed. We demonstrate that the overexpression of both <italic>SOD1</italic> and <italic>SOD1<sup>G93A</sup></italic> 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.</p>