Using an advanced intercross line to identify quantitative trait loci controlling immune response during collagen-induced arthritis.

Advanced intercross line (AIL) is a powerful tool for high-resolution mapping of quantitative trait loci (QTLs). Several AILs have been generated to refine QTLs since the method was proposed about a decade ago. However, no AIL has been used for identifying novel QTLs. Here we used an AIL to test this possibility. We genotyped 308 (DBA/1 x FVB/N) F(11/12) AIL mice with 109 informative markers covering four chromosomes, with an average intermarker distance of 5.5 Mb. Several normally distributed quantitative traits involved in the immune response during the course of collagen-induced arthritis (CIA), such as anti-collagen II antibodies, T-cell subset proportions and reactive oxygen species (ROS) production were taken as phenotypes. Four QTLs, namely Ciaa1, Lctlp1, Lctlp2 and Rosq1, controlling anti-collagen II IgG2a levels, lymph nodes CD8(+) T cell proportion and ROS production were identified with support intervals of 15, 14, 8 and 8 Mb, respectively. Alleles of Lctlp1 and Lctlp2 suppressing CD8(+) T cell proportion as well as the Rosq1 allele enhancing ROS production were correlated with higher CIA severity scores. Taken together, we successfully used an AIL to identify novel QTLs controlling immune responses during CIA with relatively small support intervals.