Polymorphism of the mouse gene for the interleukin 10 receptor alpha chain (Il10ra) and its association with the autoimmune phenotype.
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.
Qi
Zan-Mei
ZM
Central Laboratory, the First Affiliated Hospital, China Medical University, 155 Nan-Jing Bei, Shenyang, Liaoning, 110001, PR China.
Wang
Jun
J
Sun
Zheng-Rong
ZR
Ma
Feng-Mao
FM
Zhang
Qing-Rui
QR
Hirose
Sachiko
S
Jiang
Yi
Y
D000818:Animals; D003433:Crosses, Genetic; D017931:DNA Primers; D020022:Genetic Predisposition to Disease; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D010641:Phenotype; D011110:Polymorphism, Genetic; D021122:Protein Subunits / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics*; D053701:Receptors, Interleukin-10; D013045:Species Specificity
D017931:DNA Primers; D021122:Protein Subunits; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10