Genomic dissection and prioritizing of candidate genes of QTL for regulating spontaneous arthritis on chromosome 1 in mice deficient for interleukin-1 receptor antagonist

Abstract

Rheumatoid arthritis is a heterogeneous disease with clinical and biological polymorphisms. IL-1RN is a protein that binds to interleukin-1 (IL-1) receptors and inhibits the binding of IL-1-alpha and IL-1-beta. IL-1RN levels are elevated in the blood of patients with a variety of infectious, immune, and traumatic conditions. Balb/c mice deficient in IL-1ra (mouse gene of IL-1RN) develop spontaneous autoimmune arthritis while DBA/1 mice deficient in IL-1ra do not. Previously, we identified a major QTL that regulates the susceptibility to arthritis in Balb/c mice with IL-1ra deficiency. In this study, we found that the QTL may contain two peaks that are regulated by two sets of candidate genes. By haplotype analysis, the total genomic regions of candidate genes were reduced from about 19 Mbp to approximately 9 Mbp. The total number of candidate genes was reduced from 208 to 21.