The genetic susceptibility to collagen-induced arthritis (CIA) in mice
, the most commonly used model for rheumatoid arthritis, has been anal
yzed. The highly susceptible B10.RIII strain was crossed with the resi
stant RIIIS/J strain and the F2 intercross mice were subjected to geno
mic screening using microsatellite markers. These strains share the MH
C region on chromosome 17, known to be of importance in CIA (this locu
s is named Mcia1). The same cross has earlier been used to map the maj
or genes outside the MHC controlling chronic relapsing experimental al
lergic encephalomyelitis (EAE). It was found that the major locus cont
rolling CIA (Mcia2; lod 4.12) was located on chromosome 3 in the same
region as one of the major loci controlling EAE (Eae3). The linkage wa
s reproduced in a mouse strain in which the locus was isolated on the
B10.RIII background at the N412 generation. A second putative locus wa
s identified on chromosome 13 (lod 3.13). The present finding identifi
es new loci outside the MHC controlling CIA and provides evidence that
mouse CIA is controlled by polymorphic genes.