Slc11a1 (formerly NRAMP1) gene modulates both acute inflammatory reactions and pristane-induced arthritis in mice.
Mice selected for the maximum acute inflammatory reaction (AIRmax) are highly susceptible to pristane-induced arthritis (PIA), whereas mice selected for the minimum response (AIRmin) are resistant. These lines show distinct patterns of leukocyte infiltration and R and S allele frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) gene. In order to study the interactions of the Slc11a1 R and S alleles with the inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax(RR), AIRmax(SS), AIRmin(RR) and AIRmin(SS) lines were produced by genotype-assisted breedings. These mice received two intraperitoneal injections of 0.5 ml pristane at 60-day intervals, and the subsequent development of arthritis was assessed for 210 days. Cytokine-secreting cell profiles were investigated using enzyme-linked immunospot. Arthritis incidence in AIRmax(RR) mice reached 29%, whereas PIA incidence in AIRmax(SS) mice was 70% by day 180. AIRmin(RR) mice were resistant, whereas 13.3% of AIRmin(SS) mice became arthritic. The presence of the defective S allele also increased arthritis severity, although acute inflammation was higher in mice bearing the R allele. A predominant Th0/Th2-type response in Slc11a1(SS) mice was observed. These results indicate that Slc11a1 is a strong candidate for the QTL modulating acute inflammation and for PIA.
Peters
L C
LC
Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.
Jensen
J R
JR
Borrego
A
A
Cabrera
W H K
WH
Baker
N
N
Starobinas
N
N
Ribeiro
O G
OG
Ibañez
O M
OM
De Franco
M
M
D000483:Alleles; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D027682:Cation Transport Proteins / Q000235:genetics*; D033481:Chromosomes, Mammalian; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018895:Microsatellite Repeats; D040641:Quantitative Trait Loci; D013154:Spleen / Q000166:cytology; D013729:Terpenes; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D016207:Cytokines; D013729:Terpenes; D000099173:Natural Resistance-associated Macrophage Protein 1; C009042:pristane