Identification of collagen-induced arthritis loci in aged multiparous female mice |
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Authors: | Maria Liljander Mary-Ann Sällström Sara Andersson Åsa Andersson Rikard Holmdahl Ragnar Mattsson |
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Affiliation: | (1) Lund Transgenic Core Facility, Lund University, Lund, Sweden;(2) Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark;(3) Medical Inflammation Research, Lund University, Lund, Sweden |
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Abstract: | Collagen-induced arthritis in mice is one of the most commonly used autoimmune experimental models, with many similarities
to rheumatoid arthritis. Since collagen-induced arthritis is a complex polygenic disease there is a need for identification
of several major disease-controlling genes. Because rheumatoid arthritis particularly affects aged women, we have in the present
study identified new genetic regions critical for collagen-induced arthritis by studying aged female mice of a cross between
NFR/N and B10.Q (H-2q haplotype). The mice in the present study had different reproductive histories, which did not significantly affect the onset,
incidence or severity of the disease. A total of 200 female mice were used in a total genome-wide screening with 125 microsatellite
markers. We found one new significant quantitative trait locus affecting the arthritis incidence, severity and day of onset
on chromosome 11 (denoted Cia40), which colocalizes with a locus controlling pregnancy failure. Furthermore, a quantitative trait locus of suggestive significance
associated with the incidence, severity and day of onset was identified on chromosome 1. Finally, a suggestively significant
quantitative trait locus associated with collagen type II antibody titers was identified on chromosome 13. This study indicates
that several gene loci control arthritis in aged multiparous females, and that at least one of these loci coincides with pregnancy
failure. |
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