Increased susceptibility to collagen-induced arthritis in female mice carrying congenic Cia40/Pregq2 fragments

Maria Liljander¹ , Åsa Andersson² , Rikard Holmdahl³^,4 and Ragnar Mattsson¹

¹Lund Transgenic Core Facility, BMC C13, Lund University, Klinikgatan 28, SE-221 84 Lund, Sweden

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

³Medical Inflammation Research, Lund University, BMC I11, SE-221 84 Lund, Sweden

⁴Karolinska Institute, Division of Medical Inflammation Research, Sheeles väg 2, SE-171 77 Stockholm, Sweden

author email corresponding author email

Arthritis Research & Therapy 2008, 10:R88doi:10.1186/ar2470


Published:	6 August 2008

Abstract

Introduction

Collagen-induced arthritis (CIA) in mice is a commonly used experimental model for rheumatoid arthritis (RA). We have previously identified a significant quantitative trait locus denoted Cia40 on chromosome 11 that affects CIA in older female mice. This locus colocalizes with another locus, denoted Pregq2, known to affect reproductive success. The present study was performed to evaluate the role of the Cia40 locus in congenic B10.Q mice and to identify possible polymorphic candidate genes, which may also be relevant in the context of RA.

Methods

Congenic B10.Q mice carrying an NFR/N fragment surrounding the Cia40/Pregq2 loci were created by 10 generations of backcrossing (N10). The congenic mice were investigated in the CIA model, and the incidence and severity of arthritis as well as the serum levels of anti-collagen II (CII) antibodies were recorded.

Results

Significant effects on onset, incidence, severity, and anti-CII antibody titers were observed in female mice carrying a heterozygous congenic Cia40/Pregq2 fragment of NFR/N origin, containing one or more polymorphic genes. Congenic male mice did not show increased incidence of CIA, but males carrying a heterozygous fragment showed a significant increase in severity in comparison with wildtype B10.Q males (littermates).

Conclusion

The Cia40/Pregq2 locus at chromosome 11 contains one or more polymorphic genes of NFR/N origin that significantly influence both incidence and severity of CIA in heterozygous congenic mice of the B10.Q strain. The major polymorphic candidate genes for the effects on CIA are Cd79b, Abca8a, and Map2k6. The congenic fragment also contains polymorphic genes that affect reproductive behavior and reproductive success. The Sox9 gene, known to influence sex reversal, is a candidate gene for the reproductive phenotype.