Animal models of ankylosing spondylitis

The pathology of ankylosing spondylitis (AS) and related spondyloarthropathies (SpA) characteristically involve a sacroiliitis and inflammation of the intervertebral discs (IVD) in the lumbar spine, and an enthesitis at sites of ligamentous insertions into bone. The proteoglycans aggrecan and versican are large molecules that aggregate with hyaluronic via a globular 1 domain. These domains share significant homology at the level of B and T cell epitope recognition. Both proteoglycans are present in the intervertebral disc and hyaline cartilages of the sacroiliac joint, as well as in entheses. Whereas aggrecan is most concentrated in the nucleus of the IVD and in articular cartilages and endplates, versican is generally absent from these tissues except in the sacroiliac joint, but is concentrated in ligaments and the annulus. Immunity to these molecules in BALB/c mice results in an AS-like pathology, including sacroiliitis, enthesitis, and discitis. The pathology of AS is closely associated with the expression of the class I molecule human leukocyte antigen-B27. Rats bearing this transgene develop an AS-like pathology, as well as other various signs of autoimmunity. Ankylosing spondylitis is characterized by an ankylosing pathology whereby bone formation in the annulus leads to intervertebral fusion. Mice bearing the ank/ank defect gene develop a bony ankylosis of the spine like that seen in advanced AS and related SpA. These three animal models provide insight into the pathogenesis of SpA, and opportunities to investigate their pathology in relationship to human disease where investigation of the pathobiology is very difficult, because of restricted access to involved tissues.