Experiment
Linkage analysis was performed on 100 (BXD2/TyJ x DBA/2J)F2 intercross animals and 15 (BXD2/TyJ x C57BL/6J)F2 animals to identify QTLs associated with arthritis phenotypes. Parental strain BXD2/TyJ spontaneously develops lupus and erosive arthritis phenotypes in adult life, and more females (66%) than males (42%) are affected. Among the F2 animals 6.1% developed only arthritis, 20.1% developed only increased urinary albumin, and 6.1% developed both arthritis and increased urinary albumin. A panel of 620 microsatellite marker genotype information on the BXD series of recombinant inbred strains was used for linkage analysis.
A locus named Erars1 (erosive arthritis susceptibility 1) shows linkage to serum anti-DNA antibody levels at 78 cM on mouse Chromosome 2 near D2Mit412 (163 Mb). The DBA/2J-derived allele at Erars1 confers increased serum titers of anti-DNA antibodies. A previously identified arthritis QTL named Rends at 86 cM maps near Erars1.
A locus named Erars2 (erosive arthritis susceptibility 2) shows linkage to increased levels of serum rheumatoid factor at 53.6 cM on mouse Chromosome 4 near D4Mit146 (109 Mb). C57BL/6J-derived alleles at Erar2 confer increased serum titers of rheumatoid factor. Previously identified lupus and autoimmune QTL mapping near Erars2 are Adaz1 (49.6 cM), Arvm2 (58 cM), Asm2 (51 cM), Im2 (51 cM), Lbw2 (55.6 cM), Lmb1 (57.5 cM), Sles2 (58 cM), and Spm1 (49 cM).
Analysis Tools