An Accidental Discovery of a New Potential Mouse Model of the Axial Spondyloarthritis

Abstract

Abstract Many preclinical mouse models of arthritis exists but none of the axial spondyloarthritides (axSpA) mouse model to examine the pathogenic mechanism(s) and the effect of drugs. Collagen antibody induced arthritis (CAIA) is one of the most widely used mouse model of arthritis and it is complement-dependent. We found in 100s of mice developing CAIA also developed axSpA. To induce CAIA in mice, at day 0, mice were injected intraperitoneally with anti-collagen antibodies, followed by lipopolysaccharide injection at day 3. On day 10, mice were sacrificed and assessed according to gross spinal morphology and paw synovitis scores. CAIA mice demonstrated an exaggerated kyphosis through the spine, as well as hypertrophic cartilage and osseous damage of the intravertebral joints. ImmunoHistoChemical staining of the kyphotic area revealed increased complement C3 staining and macrophage staining, with localization to the intravertebral joint margins. In vivo imaging showed that anti-collagen antibodies-conjugated with IRDye® 800CW not only localized to cartilage surface in the joints but also in the spine in arthritic mice. Thus CAIA exhibited salient features of axSpA therefore it could be a by-product of autoimmune arthritis. This new mouse model of axSpA may allow investigators to shed light on the basic aspects of axSpA development and treatment.