Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis.
Two autoimmune murine models--proteoglycan (aggrecan)-induced arthritis (PGIA) and collagen-induced arthritis (CIA)--were developed in parent strains, F1 and F2 hybrids of major histocompatibility complex (MHC)-matched (H-2) BALB/c x DBA/2 and MHC-unmatched (H-2/H-2) BALB/c x DBA/1 intercrosses. The major goal of this comparative study was to identify disease (model)-specific (PGIA or CIA) and shared clinical and immunologic loci in 2 types of genetic intercrosses. Qualitative (binary/susceptibility) and quantitative (severity and onset) clinical trait loci were separated and analyzed independently or together with various pathophysiologic/immunologic traits, such as antigen-specific T- and B-cell responses and cytokine production. The major quantitative trait locus (QTL) was the MHC on chromosome 17, which was especially dominant in CIA. In addition, chromosomes 3, 5, 10, and X contained shared clinical loci in both models, and a total of 8 QTLs (clinical traits together with immunologic traits) were colocalized in PGIA and CIA.
Glant
T T
TT
Departments of Orthopedic Surgery and Biochemistry, Rush University at Rush-Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612, USA. tglant@rush.edu
Adarichev
V A
VA
Nesterovitch
A B
AB
Szanto
S
S
Oswald
J P
JP
Jacobs
J J
JJ
Firneisz
G
G
Zhang
J
J
Finnegan
A
A
Mikecz
K
K
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004198:Disease Susceptibility; D008040:Genetic Linkage; D006801:Humans; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011509:Proteoglycans / Q000276:immunology / Q000633:toxicity*; D040641:Quantitative Trait Loci; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D016207:Cytokines; D011509:Proteoglycans