title: Copper-zinc superoxide dismutase-deficient mice show increased susceptibility to experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein 35-55.
abstract: In this report, we have addressed the role of copper-zinc superoxide dismutase (SOD1) deficiency in the mediation of central nervous system autoimmunity. We demonstrate that SOD1-deficient C57Bl/6 mice develop more severe autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein (MOG) 35-55, compared with wild type mice. This alteration in the disease phenotype was not due to aberrant expansion of MOG-specific T cells nor their ability to produce inflammatory cytokines; rather lymphocytes generated in SOD1-deficient mice were more prone to spontaneous cell death when compared with their wild type littermate controls. The data point to a role for SOD1 in the maintenance of self-tolerance leading to the suppression of autoimmune responses.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
authors.forename: Chandirasegaran
authors.initials: C
authors.lastname: Massilamany
authors.forename: Arunakumar
authors.initials: A
authors.lastname: Gangaplara
authors.forename: Heejeong
authors.initials: H
authors.lastname: Kim
authors.forename: Charlotte
authors.initials: C
authors.lastname: Stanford
authors.forename: Govardhan
authors.initials: G
authors.lastname: Rathnaiah
authors.forename: David
authors.initials: D
authors.lastname: Steffen
authors.forename: Jaekwon
authors.initials: J
authors.lastname: Lee
authors.forename: Jay
authors.initials: J
authors.lastname: Reddy
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D015704:CD4 Antigens / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D005620:Freund's Adjuvant / Q000633:toxicity; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics; D010446:Peptide Fragments / Q000633:toxicity; D013482:Superoxide Dismutase / Q000172:deficiency*; D000072105:Superoxide Dismutase-1; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D003609:Dactinomycin; C025942:7-aminoactinomycin D; D005620:Freund's Adjuvant; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1