Identification of new quantitative trait loci in mice with collagen-induced arthritis

摘要: Objective Collagen-induced arthritis (CIA) in the mouse is one of most widely used autoimmune experimental models, with many features similar to rheumatoid arthritis. This study sought identify potential genetic regulatory mechanisms CIA major histocompatibility complex–matched (H2-q) F2 hybrid mice. Methods We 126 polymorphic markers perform simple sequence-length polymorphism analysis on 290 hybrids arthritis-susceptible (DBA/1J) and arthritis-resistant (FVB/N) inbred strains. The clinical traits (disease severity onset) were assessed, serum antibodies specific type II collagen (CII) determined by enzyme-linked immunosorbent assay 270 mice. Lymph nodes from 94 mice test ratio CD4 CD8 fluorescence-activated cell sorter analysis, proliferation was XTT test. Results Two quantitative trait loci (QTLs) identified previous studies confirmed; these severity-controlling Cia2 onset-controlling Cia4 chromosome 2. Moreover, we 5 new QTLs, 1 for CII-specific IgG2a 5, 2 controlling IgG1 antibody response chromosomes 10 13, CD4:CD8 2, (measured test) 16. Complement component C5 as probable main candidate gene QTLs Cia4. carrying a 2-basepair deletion C5, FVB/N allele, had low incidence less severe disease compared those DBA/1J allele. Conclusion This genome scan provides additional evidence confirming role loci, identifies