Genetic control of collagen-induced arthritis in a cross with NOD and C57BL/10 mice is dependent on gene regions encoding complement factor 5 and Fc gamma RIIb and is not associated with loci controlling diabetes

The nonobese diabetic (NOD) mouse spontaneously develops autoimmune-mediate d diseases such as diabetes and Sjogren's syndrome. To investigate whether NOD genes also promote autoimmune-mediated arthritis we established a NOD s train with an MHC class II fragment containing the A(q) class II gene predi sposing for collagen induced arthritis (NOD.Q). However, this mouse was res istant to arthritis in contrast to other A(q) expressing strains such as B1 0.Q and DBA/1. To determine the major resistance factor/s, a genetic analys is was performed. (NOD.QxB10.Q)F1 mice were resistant, whereas 27% of the ( NOD.QxB10.Q)F2 mice developed severe arthritis. Genetic mapping of 353 F2 m ice revealed two loci associated with arthritis. One locus was found on chr omosome 2 (LOD score 9.8), at the location of the complement factor 5 (C5) gene. The susceptibility allele was from B10.Q, which contains a productive C5 encoding gene in contrast to NOD.Q. The other significant locus was fou nd on chromosome 1 (LOD score 5.6) close to the Fc-gamma receptor IIb gene, where NOD carried the susceptible allele. An interaction between the two l oci was observed, indicating that they operate on the same or on interactin g pathways. The genetic control of arthritis is unique in comparison to dia betes, since none of these loci have been identified in analysis of diabete s susceptibility.