Pristane-induced arthritis loci interact with Slc11a1 gene to determine susceptibility in mice selected for high inflammation
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1
Instituto Butantan, Brazil
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2
Fondazione IRCCS Istituto Nazionale dei Tumori, Italy
AIRmax (maximal inflammation) and AIRmin (minimal inflammation) mice show distinct susceptibility to pristane-induced arthritis (PIA). Slc11a1, which regulates macrophage and neutrophil activity, is involved in this disease. AIRmaxSS mice homozygous for the non-functional Slc11a1 S (gly169asp) allele are more susceptible than the other lines. The aim of this work was to identify genes in acute inflammatory reaction loci that interact with Slc11a1 alleles to modulate PIA. Mice received two ip injections of 0.5 mL pristane with 60 days of interval. Global gene expression analysis was performed on Affymetrix mouse 1.0 ST bioarrays (27k genes) using RNA (n=4) from arthritic or control paws. In parallel, genome wide linkage studies were performed to search for arthritis QTL in an F2 (AIRmax x AIRmin, n=290) population. Significant (LODscore > 4) arthritis QTL on chromosomes 5 and 8, and suggestive QTL on chromosomes 7, 17 and 19 were detected. Global gene expression analysis demonstrated significantly (P<0.001) over-represented genes related to inflammatory response and chemotaxis in AIRmaxRR and AIRmaxSS mice, as well as in the AIRmax heterozygous group. Higher up-regulation of chemokine genes Cxcl1, Cxcl9, Cxcl5, Cxcl13 on chromosome 5 was observed in AIRmaxSS than in the other lines. In chromosome 8, macrophage scavenger receptor 1 and heme oxigenase (decycling) 1 genes were also more expressed in AIRmaxSS mice. RT-qPCR experiments validated microarray analyses. Results revealed that the gene expression profile of two arthritis QTL (on chromosomes 5 and 8) correlates with Slc11a1 alleles, resulting in enhanced AIRmaxSS mice susceptibility to PIA.
Acknowledgements
Finantial Support: The State of São Paulo Research Foundation (FAPESP) and National Council of Research (CNPq), Brasil.
Keywords:
mice genetically selected,
pristane-induced arthritis (PIA),
global gene expression,
QTL analysis,
Inflammation
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
De Franco
M,
Correa
M,
Borrego
A,
Jensen
JR,
Cabrera
WH,
Starobinas
N,
Ribeiro
OG,
Galvan
A,
Dragani
TA and
Ibañez
OM
(2013). Pristane-induced arthritis loci interact with Slc11a1 gene to determine susceptibility in mice selected for high inflammation.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00419
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Received:
18 Apr 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Marcelo De Franco, Instituto Butantan, Sao Paulo, Brazil, mdfranco@butantan.gov.br