Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes
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ABSTRACT: INTRODUCTION: In a cross between the susceptible B10.RIII (H-2r) and resistant RIIIS/J (H-2r) mouse strains, a locus on mouse chromosome 5 (Eae39) was previously shown to control experimental autoimmune encephalomyelitis (EAE). Recently, quantitative trait loci (QTL), linked to disease in different experimental arthritis models were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to experimental autoimmune encephalomyelitis , control development of collagen induced arthritis (CIA). METHODS: Collagen induced arthritis, induced by immunization with bovine type II collagen, was studied in Eae39 congenic- and sub-interval congenic mice. Antibody titers were investigated with ELISA. Gene-typing was performed by micro-satellite mapping and statistics was calculated by standard methods. RESULTS: Collagen induced arthritis experiments with Eae39 congenic- and sub-interval congenic mice, carrying RIIIS/J genes on the B10.RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titers. Two of the loci promoted disease and the third locus was protecting from collagen induced arthritis development. By further breeding of mice with small congenic fragments, we identified a 3.2 Megabasepair (Mbp) interval that regulates disease. CONCLUSIONS: Disease promoting- and protecting genes within the Eae39 locus on mouse chromosome 5, control susceptibility to collagen induced arthritis. A disease-protecting locus in the telomeric part of Eae39 results in lower anti-collagen antibody responses. The study shows the importance of breeding sub-congenic mouse strains to reveal genetic effects on complex diseases.
|Journal||Arthritis Research & Therapy|
|Publication status||Published - 2009|
- Former Faculty of Pharmaceutical Sciences