TY - JOUR
T1 - A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen
AU - Xue, Dahai
AU - Shi, Hong
AU - Smith, James D.
AU - Chen, Xinguo
AU - Noe, Dennis A.
AU - Cedervall, Tommy
AU - Yang, Derek D.
AU - Eynon, Elizabeth
AU - Brash, Douglas E.
AU - Kashgarian, Michael
AU - Flavell, Richard A.
AU - Wolin, Sandra L.
PY - 2003/6/24
Y1 - 2003/6/24
N2 - 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.
AB - 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.
U2 - 10.1073/pnas.0832411100
DO - 10.1073/pnas.0832411100
M3 - Article
C2 - 12788971
AN - SCOPUS:0038272058
SN - 0027-8424
VL - 100
SP - 7503
EP - 7508
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -