title: Lack of TDP-43 abnormalities in mutant SOD1 transgenic mice shows disparity with ALS.
abstract: Mislocalization of the TAR-DNA binding protein (TDP-43) from the nucleus to the cytoplasm of diseased motor neurons and association with intraneuronal ubiquitinated inclusions has recently been reported in amyotrophic lateral sclerosis (ALS). Here, we have investigated TDP-43 immunoreactivity in three lines of mutant SOD1 transgenic mice, G93A, G37R and G85R and compared with labeling in one sporadic ALS case and two familial ALS cases carrying mutations in SOD1, A4T and I113T. Our findings show that there is no mislocalization of TDP-43 to the cytoplasm in motor neurons of mutant SOD1 transgenic mice, nor association of TDP-43 with ubiquitinated inclusions. In contrast, mislocalization of TDP-43 to the cytoplasm and association with ubiquitinated inclusions was found in the ALS cases, including those carrying mutations in SOD1. Interestingly, there was no association of TDP-43 with ubiquitinated hyaline conglomerate inclusions, pathology closely associated with ALS cases carrying mutations in SOD1. Our findings indicate that the process of motor neuron degeneration in mutant SOD1 transgenic mice is unlikely to involve the abnormalities of TDP-43 described in the human disease.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, Department of Laboratory, Medicine and Pathobiology, University of Toronto, Toronto, Canada M5S 3H2. jan.robertson@utoronto.ca
authors.forename: Janice
authors.initials: J
authors.lastname: Robertson
authors.forename: Teresa
authors.initials: T
authors.lastname: Sanelli
authors.forename: Shangxi
authors.initials: S
authors.lastname: Xiao
authors.forename: Wencheng
authors.initials: W
authors.lastname: Yang
authors.forename: Patrick
authors.initials: P
authors.lastname: Horne
authors.forename: Robert
authors.initials: R
authors.lastname: Hammond
authors.forename: Erik P
authors.initials: EP
authors.lastname: Pioro
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Strong
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D021381:Protein Transport / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D004268:DNA-Binding Proteins; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1