Experiment
H2 congenic strains B10.RIII/Lund-H2r and B10.Q/Lund-H2q are highly susceptible to collagen-induced arthritis (CIA). Congenic B10.RIII/Lund-H2r is derived from CIA resistant donor strain RIII/WySn-H2r and CIA susceptible background strain C57BL/10Sn-H2b. Congenic B10.Q/Lund-H2q is derived from donor strain DBA/1-H2q and background strain C57BL/10Sn-H2b. These 2 congenics should only differ from their background strains at the H2 locus. However, genome scan using 150 microsatellite markersrevealed RIII/WySn contamination on a segment of mouse Chromosome 10 from D10Mit196 (31 cM) to D10Mit178 (59 cM) in the B10.RIII/Lund-H2r congenic. This locus coincides with Cia8 and is designated Cia39.
A new congenic was created by introgressing an RIII/WySn-derived Cia39 interval onto the genetic background of B10.Q/Lund-H2q. The reciprocal congenic was also created in which a C57BL/10Sn-derived Cia39 interval from donor strain B10.Q/Lund-H2q was introgressed onto the genetic background of B10.RIII/Lund-H2r. As expected, the RIII/WySn-derived Cia39 interval significantly increased CIA incidence and severity on the B10.Q/Lund-H2q background while the C57BL/10-derived Cia39 interval decreased CIA incidence and severity on the B10.RIII/Lund-H2r background. This finding suggests that Cia39 in conjunction with the H2 interval on mouse Chromosome 17 influences CIA susceptibility. Cia39 appears to have an additive effect.
Potential candidate genes mapping near Cia39 are Bsg (42.4 cM), Lilrb4(32cM),Ostm1 (29 cM), Prf1 (36 cM), Mif (40.9 cM), Mmp11 (40.9 cM), Aire (41.6 cM), Timp3 (47 cM), Itgb2 (41.5 cM), Igf1 (48 cM), and Socs2 (52 cM).
Previously identified arthritis QTLs mapping near Cia39 are Pgia6 (12 cM), Eae17 (36 cM), Asm1 (39 cM), Lmb4(41 cM),Asthm1 (44 cM), and Bbaa18 (31.5 cM).
Several autoimmune QTLs have been mapped to the H2 locus on mouse Chromosome 17. These QTLs include Cia1, Pgia17, Bbaa8, Eae1, Eae5, Sles1, Asbb3, Mbis4, Orch1, Cdcs5, Ssial4, and Idd1.