Abstract |
Several studies suggest that interleukin (IL)-10 pathway is involved in murine lupus, while no linkage of IL-10 gene polymorphism to disease susceptibility has been reported in studies with lupus-prone mice. Since IL-10 functions through the specific IL-10 receptor alpha (IL-10RA) chain and the IL-10RA gene (Il10ra) is linked to the susceptibility loci of atopic dermatitis and Crohn's disease identified using mouse models, we supposed that IL-10RA might be involved in murine lupus. By flow cytometry analysis, we found that NZW mice, one of the parental strains of lupus-prone (NZBxNZW) F1 mice, express extremely low levels of IL-10RA compared with NZB mice, the other parental strain, and the healthy BALB/c and C57BL/6 mice. Sequence analyses of Il10ra cDNA of NZW mice showed multiple nucleotide mutations compared with that of NZB and C57BL/6 strains, some of which would result in amino acid substitutions in the IL-10RA protein. Lupus-prone MRL mice shared the same polymorphism with NZW. Analyses using (NZBxNZW) F1xNZB backcross mice showed that high serum levels of IgG antichromatin antibodies were regulated by a combinatorial effect of the NZW Il10ra allele and a heterozygous genotype for Tnfa microsatellite locus. Our data suggest that the polymorphic NZW-type Il10ra may be involved in the pathologic production of antichromatin antibodies and, if so, may contribute in part to the development of systemic lupus erythematosus as one susceptibility allele.
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Authors | Zan-Mei Qi, Jun Wang, Zheng-Rong Sun, Feng-Mao Ma, Qing-Rui Zhang, Sachiko Hirose, Yi Jiang |
Journal | Immunogenetics
(Immunogenetics)
Vol. 57
Issue 9
Pg. 697-702
(Oct 2005)
ISSN: 0093-7711 [Print] United States |
PMID | 16160826
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Primers
- Protein Subunits
- Receptors, Interleukin
- Receptors, Interleukin-10
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Topics |
- Animals
- Crosses, Genetic
- DNA Primers
- Genetic Predisposition to Disease
- Lupus Erythematosus, Systemic
(genetics, immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Inbred MRL lpr
- Mice, Inbred NZB
- Phenotype
- Polymorphism, Genetic
- Protein Subunits
(genetics)
- Receptors, Interleukin
(biosynthesis, genetics)
- Receptors, Interleukin-10
- Species Specificity
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