title: The SOD1 transgene expressed in erythroid cells alleviates fatal phenotype in congenic NZB/NZW-F1 mice.
abstract: Oxidative stress due to a superoxide dismutase 1 (SOD1) deficiency causes anemia and autoimmune responses, which are phenotypically similar to autoimmune hemolytic anemia (AIHA) and systemic lupus erythematosus (SLE) in C57BL/6 mice and aggravates AIHA pathogenesis in New Zealand black (NZB) mice. We report herein on an evaluation of the role of reactive oxygen species (ROS) in a model mouse with inherited SLE, that is, F1 mice of the NZB × New Zealand white (NZW) strain. The ROS levels within red blood cells (RBCs) of the F1 mice were similar to the NZW mice but lower compared to the NZB mice throughout adult period. Regarding SLE pathogenesis, we examined the effects of an SOD1 deficiency or the overexpression of human SOD1 in erythroid cells by establishing corresponding congenic F1 mice. A SOD1 deficiency caused an elevation in ROS production, methemoglobin content, and hyperoxidation of peroxiredoxin in RBC of the F1 mice, which were all consistent with elevated oxidative stress. However, while the overexpression of human SOD1 in erythroid cells extended the life span of the congenic F1 mice, the SOD1 deficiency had no effect on life span compared to wild-type F1 mice. It is generally recognized that NZW mice possess a larval defect in the immune system and that NZB mice trigger an autoimmune reaction in the F1 mice. Our results suggest that the oxidative insult originated from the NZB mouse background has a functional role in triggering an aberrant immune reaction, leading to fatal responses in F1 mice.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuki
authors.forename: Tasuku
authors.initials: T
authors.lastname: Konno
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kurahashi
authors.forename: Saori
authors.initials: S
authors.lastname: Suzuki
authors.forename: Jaeyong
authors.initials: J
authors.lastname: Lee
authors.forename: Futoshi
authors.initials: F
authors.lastname: Okada
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Iuchi
authors.affiliation: a Department of Biochemistry and Molecular Biology , Graduate School of Medical Science, Yamagata University , Yamagata , Japan.
authors.forename: Takujiro
authors.initials: T
authors.lastname: Homma
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D041905:Erythroid Cells / Q000166:cytology / Q000201:enzymology; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D010641:Phenotype; D000072105:Superoxide Dismutase-1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D019076:Transgenes
chemical_list: C000606291:Sod1 protein, mouse; D000072105:Superoxide Dismutase-1
keywords: Autoimmune hemolytic anemia; New Zealand white mouse; reactive oxygen species; superoxide dismutase; systemic lupus erythematosus