Finemapping of the arthritis QTL Pia7 reveals co-localization with Oia2 and the APLEC locus.
In this study, we sought to determine the effect of the quantitative trait locus Pia7 on arthritis severity. The regulatory locus derived from the arthritis-resistant E3 rat strain was introgressed into the arthritis-susceptibility DA strain through continuous backcrossing. Congenic rats were studied for their susceptibility to experimental arthritis using pristane and adjuvant oil. In addition, cell number and function of various leukocyte populations were analyzed either under naive or stimulated conditions. We found that the minimal congenic fragment of DA.E3-Pia7 rats overlapped with the minimal fragment in DA.PVG-Oia2 congenic rats, which has been positionally cloned to the antigen-presenting lectin-like receptor complex (APLEC) genes. DA.E3-Pia7 congenic rats were protected from both PIA and OIA, but the protection was more pronounced in OIA. In adoptive transfer experiments we observed that the Pia7 locus controlled the priming of arthritogenic T cells and not the effector phase. In addition, Pia7 congenic rats had a significant higher frequency of B cells and granulocytes as well as TNFalpha production after stimulation, indicating a higher activation state of cells of the innate immune system. In conclusion, this study shows that the APLEC locus is a major locus regulating the severity of experimentally induced arthritis in rats.
Rintisch
C
C
Department of Experimental Medical Science, Lund University, Sweden.
Kelkka
T
T
Norin
U
U
Lorentzen
J C
JC
Olofsson
P
P
Holmdahl
R
R
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002874:Chromosome Mapping / Q000379:methods*; D033481:Chromosomes, Mammalian; D005260:Female; D005434:Flow Cytometry; D056426:Genetic Loci / Q000235:genetics*; D005838:Genotype; D008297:Male; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D051381:Rats; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha