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Identification of acute inflammatory response loci involved on pristane-induced arthritis development in mice genetically selected.

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Author(s):
Luciana Carla Oliva Marques Peters
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Marcelo de Franco; Niels Olsen Saraiva Câmara; Alexandre de Castro Keller; Sonia Jancar Negro; Silvio Luis de Oliveira
Advisor: Marcelo de Franco
Abstract

AIRmax and AIRmin mice homozygous for Slc11a1 R and S allele were evaluated for pristane-induced arthritis (PIA) susceptibility. The presence of S allele increased the incidence and the arthritis severity in ARmax mice, suggesting that Slc11a1 or other closed-linked gene interacts with inflammatory loci to modulate PIA. In order to identify inflammatory modifier loci modulating experimental arthritis development, genotype-phenotype association studies and global gene expression analyses were performed. Mice received i.p. injections of pristane and the paw RNAs were isolated at day 180. Global gene expression analysis was performed on Codelink bioarrays (36k genes) and validated by real time PCR. The microsatellite polymorphism analyses were performed using MapManager program. Two regions on chromosomes 1 and 11 were identified. Higher number of differentially-expressed genes were detected in AIRmax SS subline, which significant over-represented biological themes were related to inflammatory response and chemotaxis. Susceptible AIRmax SS mice also display high up-regulation of Ccl3, Ccl7, C3ar1, Il10, Stat3, Tirap, Trem 1, Trem 3, Mefv, Ptx3, Chi3l3 e Kras genes. Some of them co-localize with previously identified regions mapped on chromosomes 1 and 11. (AU)