Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking ß₂-microglobulin: A model of human spondyloarthropathies

Human class I major histocompatibility complex allele HLA-B27 is associated with a group of human diseases called "spondyloarthropathies." Studies on transgenic rats expressing HLA-B27 and human 132-microglobulin have confirmed the role of HLA-B27 in disease pathogenesis. Here we report spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking ß₂- microglobulin (B27+ß₂m^-/−). In the absence of ß₂-microglobulin, B27⁺ß₂m -/- animals do not express the HLA-B27 transgene on the cell surface and have a very low level of CD8 + T cells. Most of the B27⁺ß₂m^-/− male mice showed nail changes, hair loss, and swelling in paws, which leads to ankylosis. The symptoms occur only after the B27⁺ß₂m^-/− mice are transferred from the specific pathogen-free mouse colony. These results suggest that aberrant assembly, transport, and expression of the HLA-B27 molecule may predispose an individual for development of the disease when exposed to an appropriate environmental trigger.