title: Accumulation and aggregate formation of mutant superoxide dismutase 1 in canine degenerative myelopathy.
abstract: Canine degenerative myelopathy (DM) is an adult-onset progressive neurodegenerative disorder that has recently been linked to mutations in the superoxide dismutase 1 (SOD1) gene. We generated a polyclonal antibody against canine SOD1 to further characterize the mutant SOD1 protein and its involvement in DM pathogenesis. This antibody (SYN3554) was highly specific to canine SOD1 and had the ability to reveal distinct cytoplasmic aggregates in cultured cells expressing canine mutant SOD1 and also in the spinal neurons of symptomatic homozygotes. A similar staining pattern was observed in asymptomatic homozygotes. SOD1 aggregates were not detected in the spinal neurons of heterozygotes; the accumulation of SOD1 was also detected in the reactive astrocytes of homozygotes and heterozygotes to a similar extent. Our results support the hypothesis that the cytoplasmic accumulation and aggregate formation of the mutant SOD1 protein, especially in astrocytes, are closely associated with the pathogenesis of DM. Therefore, this disease is regarded as a spontaneous large-animal model of SOD1-mediated amyotrophic lateral sclerosis in humans.
authors.affiliation: Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakamae
authors.affiliation: Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kobatake
authors.affiliation: Nippon Zenyaku Kogyo Co., Ltd., 1-1 Tairanoue, Sasagawa, Asaka-machi, Koriyama, Fukushima 963-0196, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Nippon Zenyaku Kogyo Co., Ltd., 1-1 Tairanoue, Sasagawa, Asaka-machi, Koriyama, Fukushima 963-0196, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsukui
authors.affiliation: Division of Neuropathology, Department of Pathology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori 683-8504, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.affiliation: Laboratory of Veterinary Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-8580, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Yamato
authors.affiliation: Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Urushitani
authors.affiliation: Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan. Electronic address: kamicna@gifu-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Kamishina
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000150:complications / Q000235:genetics* / Q000662:veterinary; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013118:Spinal Cord Diseases / Q000150:complications / Q000235:genetics* / Q000662:veterinary; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014162:Transfection
chemical_list: D005904:Glial Fibrillary Acidic Protein; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005982:Glutathione Transferase
keywords: Pembroke Welsh Corgis; aggregates; canine; degenerative myelopathy; superoxide dismutase 1