A genetic contamination in MHC-congenic mouse strains reveals a locus on chromosome 10 that determines autoimmunity and arthritis susceptibility.
Among the arthritis-susceptible MHC (H-2)-congenic mouse strains, B10.RIII mice are highly susceptible to collagen-induced arthritis. Surprisingly, the B10.RIII strain was also more susceptible to the T cell independent model CAIA (collagen-antibody-induced arthritis). Through genome-wide genotyping, we found that the B10.RIII and B10.Q strains differed not only in chromosome 17 (MHC) but also in a region on chromosome 10, which contained a fragment from the MHC donor RIIIS/J. We isolated the chromosome 10 as well as the chromosome 17 segments on the B10.RIII and B10.Q backgrounds. Congenic mice containing the RIIIS/J-derived chromosome 10 segment showed significantly higher susceptibility and severity of arthritis with an enhanced autoimmune response to type II collagen. Furthermore, this chromosomal segment significantly promoted CAIA. Similarly, the RIIIS/J segment in chromosome 17 also promoted CAIA independently of other gene segments. These data show that other gene regions, apart from MHC class II, may explain effects both at the priming and effector level of arthritis observed in widely used MHC congenic strains. These new congenic fragments, on both chromosome 10 and 17, provide new mouse strains suitable for studies aiming at positional cloning of new genes associated with arthritis.
Nandakumar
Kutty Selva
KS
Medical Inflammation Research, Lund University, Lund, Sweden. nan@inflam.lu.se
Holmdahl
Rikard
R
D000367:Age Factors; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology; D002874:Chromosome Mapping; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D020297:Mice, Congenic
D005819:Genetic Markers