title: A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen.
abstract: Antibodies against a conserved RNA-binding protein, the Ro 60-kDa autoantigen, occur in 24-60% of all patients with systemic lupus erythematosus. Anti-Ro antibodies are correlated with photosensitivity and cutaneous lesions in these patients and with neonatal lupus, a syndrome in which mothers with anti-Ro antibodies give birth to children with complete congenital heart block and photosensitive skin lesions. In higher eukaryotes, the Ro protein binds small RNAs of unknown function known as Y RNAs. Because the Ro protein also binds misfolded 5S rRNA precursors, it is proposed to function in a quality-control pathway for ribosome biogenesis. Consistent with a role in the recognition or repair of intracellular damage, an orthologue of Ro in the radiation-resistant eubacterium Deinococcus radiodurans contributes to survival of this bacterium after UV irradiation. Here, we show that mice lacking the Ro protein develop an autoimmune syndrome characterized by anti-ribosome antibodies, anti-chromatin antibodies, and glomerulonephritis. Moreover, in one strain background, Ro-/- mice display increased sensitivity to irradiation with UV light. Thus, one function of this major human autoantigen may be to protect against autoantibody development, possibly by sequestering defective ribonucleoproteins from immune surveillance. Furthermore, the finding that mice lacking the Ro protein are photosensitive suggests that loss of Ro function could contribute to the photosensitivity associated with anti-Ro antibodies in humans.
authors.affiliation: Department of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Dahai
authors.initials: D
authors.lastname: Xue
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: James D
authors.initials: JD
authors.lastname: Smith
authors.forename: Xinguo
authors.initials: X
authors.lastname: Chen
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Noe
authors.forename: Tommy
authors.initials: T
authors.lastname: Cedervall
authors.forename: Derek D
authors.initials: DD
authors.lastname: Yang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Eynon
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Brash
authors.forename: Michael
authors.initials: M
authors.lastname: Kashgarian
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Wolin
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D003433:Crosses, Genetic; D004307:Dose-Response Relationship, Radiation; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics; D006579:Heterozygote; D007668:Kidney / Q000648:ultrastructure; D008177:Lupus Vulgaris / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008957:Models, Genetic; D012313:RNA / Q000378:metabolism; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins / Q000235:genetics* / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism; D013347:Subcellular Fractions; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology; D014466:Ultraviolet Rays
chemical_list: D001324:Autoantigens; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; C492050:Ssa2 protein, mouse; D012313:RNA