title: Pristane-induced arthritis loci interact with the Slc11a1 gene to determine susceptibility in mice selected for high inflammation.
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. AIRmax (SS) 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 × 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 (P<0.001) over-represented genes related to inflammatory responses and chemotaxis. Up-regulation of the chemokine genes Cxcl1, Cxcl9, Cxcl5, Cxcl13 on chromosome 5 was higher in AIRmax(SS) 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 AIRmax(SS) mice susceptibility to PIA.
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Marcelo
authors: M
authors: De Franco
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Luciana C
authors: LC
authors: Peters
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Mara A
authors: MA
authors: Correa
authors: Department of Experimental Oncology, Istituto Nazionale dei Tumori, Milan, Italy.
authors: Antonella
authors: A
authors: Galvan
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Tatiane
authors: T
authors: Canhamero
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Andrea
authors: A
authors: Borrego
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: José R
authors: JR
authors: Jensen
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Jussara
authors: J
authors: Gonçalves
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Wafa H K
authors: WH
authors: Cabrera
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Nancy
authors: N
authors: Starobinas
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Orlando G
authors: OG
authors: Ribeiro
authors: Tommaso A
authors: TA
authors: Dragani
authors: Department of Experimental Oncology, Istituto Nazionale dei Tumori, Milan, Italy.
authors: Tommaso
authors: T
authors: Dragani
authors: Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
authors: Olga M
authors: OM
authors: Ibañez
mesh_terms: D000483:Alleles; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics; D008297:Male; D051379:Mice; D040641:Quantitative Trait Loci; D013729:Terpenes; D059467:Transcriptome; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D013729:Terpenes; D000099173:Natural Resistance-associated Macrophage Protein 1; C009042:pristane