Research article

Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes

Therese Lindvall¹ , Jenny Karlsson^1,3 , Rikard Holmdahl¹ and Åsa Andersson²

¹  Department of Experimental Medical Science, Unit for Medical Inflammation Research, BMC I11, Lund University, S-221 84 Lund, Sweden

²  Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, Copenhagen University, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark

³  Current address: Pathology and Laboratory Medicine, University of California Los Angeles, 675 S. Charles E. Young Drive, Los Angeles, CA 90095, USA

author email corresponding author email

Arthritis Research & Therapy 2009, 11:R10doi:10.1186/ar2597

Published:	20 January 2009

Abstract

Introduction

In a cross between two mouse strains, the susceptible B10.RIII (H-2^r) and resistant RIIIS/J (H-2^r) 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 EAE, control development of collagen-induced arthritis (CIA).

Methods

CIA, induced by immunisation with bovine type II collagen, was studied in Eae39 congenic and sub-interval congenic mice. Antibody titres were investigated with ELISA. Gene-typing was performed by micro-satellite mapping and statistics was calculated by standard methods.

Results

Experiments of CIA in 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 titres. Two of the loci promoted disease and the third locus was protected against CIA development. By further breeding of mice with small congenic fragments, we identified a 3.2 mega base pair (Mbp) interval that regulates disease.

Conclusions

Disease-promoting and disease-protecting genes within the Eae39 locus on mouse chromosome 5 control susceptibility to CIA. 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.