Mapping of pristane induced arthritis quantitative trait loci in selection III mice

Abstract

Arthritis induced by the mineral oil pristane (pristane induced arthritis - PIA) in mice selected for high (HIII) and low (LIII) antibody production (Selection III) is a unique model, because 100% of LIII animals develop a severe arthritis resembling rheumatoid arthritis (RA) while HIII are completely resistant. We have identified a QTL (Quantitative trait locus) in chromosome 3 (Prtial), in a cosegregation study using microsatellite markers and an intercross F2 (HIII X LIII) population. This QTL is associated to susceptibility to arthritis and also regulates quantitative antibody production, which is the phenotype used for selection of these mouse lines. However, the confidence interval of this QTL is still too large to allow analysis of a reasonable number of candidate genes. New technologies like SNP based genetic mapping may allow for the narrowing of the Prtial locus and the identification of novel QTLs. A preliminary analysis, using DNA pools of animals from this intercross population in a SNP based linkage study, suggests the presence of QTLs in chromosomes 1, 3, 6, 7, 13, 14 and 19. In order to confirm the association of these regions with arthritis phenotypes, it is necessary to carry out the linkage study with the individual DNA samples, which is the main objective of our project. The DNA samples of the intercross population have already been obtained and will be analyzed by a panel containing 1449 SNPs which cover the whole genome. Then, the genotype data will be tested for association with the arthritis phenotypes, which are also available. In the regions with significant association we will investigate the differential expression of candidate genes by qRT-PCR in parental mice from both lines, either treated or not with pristane, aiming at understanding the moments and compartments where the genetic differences between the lines translate into phenotypic alterations that are relevant for resistance/susceptibility to PIA. (AU)