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Polymorphism of the mouse gene for the interleukin 10 receptor alpha chain (Il10ra) and its association with the autoimmune phenotype

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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 (NZB×NZW) 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 (NZB×NZW) F1×NZB 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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Acknowledgements

We thank Dr. Yaohua Ji of the virus Laboratory, the Second Affiliated hospital, China Medical University for providing help in using DNAstar, DNASIS, and GeneDoc software. This work was supported in part by grants 30070317 and 30170438 from the Natural Science Foundation of China.

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Author notes

  1. Zan-Mei Qi

    Present address: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, PR China

Authors and Affiliations

  1. Central Laboratory, the First Affiliated Hospital, China Medical University, 155 Nan-Jing Bei, Shenyang, Liaoning, 110001, PR China

    Zan-Mei Qi, Jun Wang, Feng-Mao Ma, Qing-Rui Zhang & Yi Jiang

  2. Key Laboratory of Immunodermatology, Ministry of Health, 155 Nan-Jing Bei, Shenyang, Liaoning, 110001, PR China

    Zan-Mei Qi, Jun Wang, Feng-Mao Ma, Qing-Rui Zhang & Yi Jiang

  3. Virus Laboratory, the Second Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China

    Zheng-Rong Sun

  4. Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan

    Sachiko Hirose

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  1. Zan-Mei Qi
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  2. Jun Wang
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  7. Yi Jiang
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Corresponding author

Correspondence to Yi Jiang.

Additional information

The Il10ra polymorphism data reported in this paper have been submitted to the Mouse Genome Informatics database and have been assigned the accession number MGI: 3528086.

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Qi, ZM., Wang, J., Sun, ZR. et al. Polymorphism of the mouse gene for the interleukin 10 receptor alpha chain (Il10ra) and its association with the autoimmune phenotype. Immunogenetics 57, 697–702 (2005). https://doi.org/10.1007/s00251-005-0036-7

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  • DOI: https://doi.org/10.1007/s00251-005-0036-7

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