Objective: To confirm the role of HLA-B2704 and hbeta(2)m gene in the pathogenesis of spontaneous inflammatory diseases by establishing HLA-B2704 and hbeta(2)m double transgenic mice model of ankylosing spondylitis. It will provide a powerful animal model for exploring the etiology, prevention and treatment of B27-relevant diseases.
Methods: The screening, identification and expression of HLA-B2704 and hbeta(2)m gene were determined by PCR, dot blot, Southern blot hybridization, RT-PCR, flow cytometry and immunohistochemistry. HE staining was performed for the diseased mice.
Results: Eight double transgenic mice bearing high copy developed spontaneous dermatosis, arthritis and nail changes in the rear paw. The results of flow cytometry in normal mice, B27 single transgenic mice, and HLA-B27/hbeta(2)m double transgenic mice were 0.63%, 7.87% and 35.87% respectively. HLA-B2704 antigen was high expressed on the cell surface, but not evident on those of B27 single transgenic mice.
Conclusions: HLA-B2704 heavy chain can induce spontaneous inflammatory diseases in the transgenic mice. Hbeta(2)m can form a stable complex with HLA-B27 and may stabilize and enhance the expression of HLA-B2704 on the cell surface.