Identification of a quantitative trait locus for spontaneous osteoarthritis in STR/ort mice

Osteoarthritis (OA) is the most common joint disorder in humans. Most of the animal models of OA were developed by surgical destabilization of joints or through transgenic approaches, and information from naturally occurring models of OA is very limited. The mouse strain STR/ort is recognized as a spontaneous model of OA. This mouse is unique in that it develops late onset cartilage degeneration of the tibio-femoral joint, similar to human OA. The purpose of this study was to identify quantitative trait loci (QTL) for the OA phenotype in STR/ort. Whereas the trait had been reported to be recessive, a significant population of the F1 generation exhibited OA phenotype. Thus, backcrossed (BC) mice generated by crossing F1 male to C57BL/6N female mice were used for genetic analysis. Degeneration of articular cartilage in BC mice was evaluated by scanning electron microscopy. Linkage analysis was carried out using microsatellite markers covering the entire genome. Cartilage degeneration in STR/ort mice was a polygenic trait. A QTL for the OA phenotype was mapped to a region 20 centimorgans proximal to the centromere of chromosome 4 (LOD = 3.37, p = 0.0065). A QTL associated with the onset of cartilage degeneration in C57BL/6N mice was also identified on chromosome 5 (LOD = 3.04, p = 0.0147). These results suggest that multiple loci are involved in the OA phenotype in mice.