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A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen

Xue, Dahai ; Shi, Hong ; Smith, James D. ; Chen, Xinguo ; Noe, Dennis A. ; Cedervall, Tommy LU ; Yang, Derek D. ; Eynon, Elizabeth ; Brash, Douglas E. and Kashgarian, Michael , et al. (2003) In Proceedings of the National Academy of Sciences of the United States of America 100(13). p.7503-7508
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences of the United States of America
volume
100
issue
13
pages
6 pages
publisher
National Academy of Sciences
external identifiers
  • scopus:0038272058
  • pmid:12788971
ISSN
0027-8424
DOI
10.1073/pnas.0832411100
language
English
LU publication?
no
id
71e240bd-c8d3-4ddb-bf17-f3a8eb17b463
date added to LUP
2022-02-10 08:18:07
date last changed
2024-02-05 20:07:25
@article{71e240bd-c8d3-4ddb-bf17-f3a8eb17b463,
  abstract     = {{Antibodies against a conserved RNA-binding protein, the Ro 60-kDa  <br>
autoantigen, occur in 24–60% of all patients with systemic lupus  <br>
erythematosus. Anti-Ro antibodies are correlated with photosensitivity <br>
and  cutaneous lesions in these patients and with neonatal lupus, a <br>
syndrome in  which mothers with anti-Ro antibodies give birth to <br>
children with complete  congenital heart block and photosensitive skin <br>
lesions. In higher eukaryotes,  the Ro protein binds small RNAs of <br>
unknown function known as Y RNAs. Because  the Ro protein also binds <br>
misfolded 5S rRNA precursors, it is proposed to  function in a <br>
quality-control pathway for ribosome biogenesis. Consistent with  a role<br>
 in the recognition or repair of intracellular damage, an orthologue of <br>
 Ro in the radiation-resistant eubacterium <em>Deinococcus radiodurans</em><br>
  contributes to survival of this bacterium after UV irradiation. Here, <br>
we show  that mice lacking the Ro protein develop an autoimmune syndrome<br>
 characterized  by anti-ribosome antibodies, anti-chromatin antibodies, <br>
and  glomerulonephritis. Moreover, in one strain background,  <em>Ro</em><sup>–</sup><sup>/</sup><sup>–</sup><br>
 mice display  increased sensitivity to irradiation with UV light. Thus,<br>
 one function of this  major human autoantigen may be to protect against<br>
 autoantibody development,  possibly by sequestering defective <br>
ribonucleoproteins from immune  surveillance. Furthermore, the finding <br>
that mice lacking the Ro protein are  photosensitive suggests that loss <br>
of Ro function could contribute to the  photosensitivity associated with<br>
 anti-Ro antibodies in humans.}},
  author       = {{Xue, Dahai and Shi, Hong and Smith, James D. and Chen, Xinguo and Noe, Dennis A. and Cedervall, Tommy and Yang, Derek D. and Eynon, Elizabeth and Brash, Douglas E. and Kashgarian, Michael and Flavell, Richard A. and Wolin, Sandra L.}},
  issn         = {{0027-8424}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{13}},
  pages        = {{7503--7508}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen}},
  url          = {{http://dx.doi.org/10.1073/pnas.0832411100}},
  doi          = {{10.1073/pnas.0832411100}},
  volume       = {{100}},
  year         = {{2003}},
}