Ifi204 as the most favored candidate gene that regulates susceptibility to spontaneous arthritis in mice deficient in IL-1ra

Abstract Aims To examine whether the increased expression level of interferon-activatable protein (Ifi) genes is associated with the decreased resistance to SAD in a congenic mouse strain DBA . B - 1 −/− which is IL1rn -deficient and contains the QTL genomic fragment associated with susceptibility to SAD, from a BALB / c −/− on the DBA / 1 −/− background. Methods We produced whole genome expression profiles from the DBA . B - 1 −/− and four parental strains, the wild type BALB / c , DBA / 1 and the IL1rn -deficient DBA / 1 −/− and BALB / c −/− . We analyzed the differential expression levels of genes in DBA . B - 1 −/− in comparison to other strains, compared these genes with that of a previous congenic strain, BALB . D1-1 −/− , which is IL1rn -deficient and contains the QTL genomic fragment associated with susceptibility to SAD, from a DBA / 1 −/− on the BALB / c −/− background and examined the candidacy of genes within the Ifi family. Results Although there are a considerable number of differentially expressed genes between DBA . B - 1 −/− and the four parental strains, the differences are in the opposite direction to that in previous comparisons between the BALB . D1-1 −/− and other strains. There were a fewer number of up-regulated genes in BALB . D1-1 −/− in comparison to DBA/1. Instead of down-regulated Ifi genes in BALB . D1-1 −/− in comparison to its parental strain BALB / c −/− , the expression levels of a few Ifi genes in the DBA . B - 1 −/− strain were higher than that of its parental strain DBA / 1 −/− . These Ifi genes are also differentially expressed between DBA . B - 1 −/− and DBA /1 strains. Their expression levels in the DBA . B - 1 −/− are similar to that in BALB / c and BALB / c −/− strains. Among these genes, only Ifi204 expressed at a significant, high level in these mouse strains. Conclusion Ifi204 is the most favored candidate gene that regulates susceptibility to spontaneous arthritis in mice deficient in IL-1ra. Both Htra1 and Dpt may be involved in the Ifi204 molecular pathway.