Identification of genes controlling collagen-induced arthritis in mice: striking homology with susceptibility loci previously identified in the rat.
The susceptibility to collagen-induced arthritis in the highly susceptible DBA/1 mouse has earlier been shown to be partly controlled by the MHC class II gene Aq. To identify susceptibility loci outside of MHC, we have made crosses between DBA/1 and the less susceptible B10.Q strain, both expressing the MHC class II gene Aq. Analysis of 224 F2 intercross mice with 170 microsatellite markers in a genome-wide scan suggested 4 quantitative trait loci controlling arthritis susceptibility located on chromosomes 6, 7, 8, and 10. The locus on chromosome 6 (Cia6), which was associated with arthritis onset, yielded a logarithm of odds score of 4.7 in the F2 intercross experiment and was reproduced in serial backcross experiments. Surprisingly, the DBA/1 allele had a recessive effect leading to a delay in arthritis onset. The suggestive loci on chromosomes 7 and 10 were associated with arthritis severity rather than onset, and another suggestive locus on chromosome 8 was most closely associated with arthritis incidence. The loci on chromosomes 7, 8, and 10 all appeared to contain disease-promoting alleles derived from the DBA/1 strain. Interestingly, most of the identified loci were situated in chromosomal regions that are homologous to regions in the rat genome containing susceptibility genes for arthritis; the mouse Cia6 locus is homologous with the rat Cia3, Pia5, Pia2, and Aia3; the locus on chromosome 7 (Cia7) is homologous with the rat Cia2; and the locus on chromosome 10 (Cia8) is homologous with the rat Cia4.
Yang
H T
HT
Beijer Laboratory, Department of Genetics and Pathology, Unit of Medical Genetics, Biomedical Center, Uppsala University, Sweden.
Jirholt
J
J
Svensson
L
L
Sundvall
M
M
Jansson
L
L
Pettersson
U
U
Holmdahl
R
R
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology*; D002874:Chromosome Mapping; D003094:Collagen / Q000276:immunology*; D003433:Crosses, Genetic; D004198:Disease Susceptibility; D005260:Female; D008040:Genetic Linkage / Q000276:immunology; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics* / Q000276:immunology*; D014644:Genetic Variation / Q000276:immunology; D016678:Genome; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019683:Penetrance; D019655:Quantitative Trait, Heritable; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
D005819:Genetic Markers; D003094:Collagen