Pristane-induced arthritis loci interact with the Slc11a1 gene to determine susceptibility in mice selected for high inflammation

Marcelo De Franco, Luciana C. Peters, Mara A. Correa, Antonella Galvan, Tatiane Canhamero, Andrea Borrego, José R. Jensen, Jussara Gonçalves, Wafa H K Cabrera, Nancy Starobinas, Orlando G. Ribeiro, Tommaso Dragani, Olga M. Ibañez

Research output: Contribution to journalArticle

Abstract

AIRmax (maximal inflammation) and AIRmin (minimal inflammation) mice show distinct susceptibilities to pristane-induced arthritis (PIA). The Slc11a1 gene, which regulates macrophage and neutrophil activity, is involved in this infirmity. AIRmaxSS mice homozygous for the non-functional Slc11a1 S (gly169asp) allele obtained by genotype-assisted crosses from AIRmax and AIRmin mice are more susceptible than mice homozygous for the Slc11a1 resistant (R) allele. The present work sought to identify the quantitative trait loci (QTL) regulating PIA and to examine the interactions of these QTL with Slc11a1 alleles in modulating PIA. Mice were given two ip injections of 0.5 mL pristane at 60 day intervals, and the incidence and severity of PIA was scored up to 160 days. Genome-wide linkage studies were performed to search for arthritis QTL in an F2 (AIRmax x AIRmin, n = 290) population. Significant arthritis QTL (LODscore>4) were detected on chromosomes 5 and 8, and suggestive QTL on chromosomes 7, 17 and 19. Global gene expression analyses performed on Affymetrix mouse 1.0 ST bioarrays (27k genes) using RNA from arthritic or control mice paws showed 419 differentially expressed genes between AIRmax and AIRmin mice and demonstrated significantly (PSS than in the other lines. Macrophage scavenger receptor 1 and hemeoxigenase (decycling) 1 genes on chromosome 8 were also expressed at higher levels in AIRmax SS mice. Our results show that the gene expression profiles of the two arthritis QTL (on chromosomes 5 and 8) correlate with Slc11a1 alleles, resulting in enhanced AIRmaxSS mice susceptibility to PIA.

Original languageEnglish
Article numbere88302
JournalPLoS One
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 5 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    De Franco, M., Peters, L. C., Correa, M. A., Galvan, A., Canhamero, T., Borrego, A., Jensen, J. R., Gonçalves, J., Cabrera, W. H. K., Starobinas, N., Ribeiro, O. G., Dragani, T., & Ibañez, O. M. (2014). Pristane-induced arthritis loci interact with the Slc11a1 gene to determine susceptibility in mice selected for high inflammation. PLoS One, 9(2), [e88302]. https://doi.org/10.1371/journal.pone.0088302