Abstract
IntroductionCollagen-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.MethodsCongenic 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.ResultsSignificant 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).ConclusionThe 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.
Highlights
Collagen-induced arthritis (CIA) in mice is a commonly used experimental model for rheumatoid arthritis (RA)
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 be relevant in the context of RA
Significant effects on onset, incidence, severity, and anti-collagen II (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
Summary
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 Cia on chromosome 11 that affects CIA in older female mice. This locus colocalizes with another locus, denoted Pregq, known to affect reproductive success. CIA shares several features with RA, there are some obvious differences between the mouse model and the human disease [1-3]. One such dissimilarity is the reversed sex susceptibility. None of the experimental autoimmune encephalitis (EAE) loci is located close to the Cia linkage peak, indicating that other polymorphic genes might be of importance
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