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Polymorphism of the mouse gene for the interleukin 10 receptor alpha chain ( Il10ra) and its association with the autoimmune phenotype.
- Source :
-
Immunogenetics . Oct2005, Vol. 57 Issue 9, p697-702. 6p. - Publication Year :
- 2005
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00937711
- Volume :
- 57
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Immunogenetics
- Publication Type :
- Academic Journal
- Accession number :
- 18579871
- Full Text :
- https://doi.org/10.1007/s00251-005-0036-7