The KRN mouse model of inflammatory arthritis.
In 1996 a new murine model of spontaneous arthritis was described by the group of Benoist and Mathis. Mice transgenic for a T cell receptor recognizing an epitope of bovine RNase and bred onto a NOD background developed severe destructive arthritis, which resembles human rheumatoid arthritis in many respects. The development of disease requires the presence of T and B lymphocytes and is dependent on the MHC class II molecule I-A(g7). B cell activation by antigen and an additional CD40-CD40 ligand interaction was found to give rise to the production of autoantibodies. Glucose-6-phosphate isomerase was identified as the target of the autoantibodies; moreover, the transgenic T cells were demonstrated to exhibit a dual specificity for both bovine RNase and glucose-6-phosphate isomerase. Importantly, the arthritis is serum transferable to normal recipients, enabling the examination of the pathogenic mechanisms of joint inflammation and destruction. Recent studies suggest the crucial involvement of the innate immune system in the development of antibody-induced arthritis. Complement components, Fc receptors and neutrophils are indispensable for disease induction. An overview of the existing data is given and the emerging concepts of the pathogenesis of the K/BxN arthritis are discussed with respect to their relevance for human rheumatoid arthritis. Because of the reliable and robust induction of joint inflammation by serum transfer this new disease model has been and will be a valuable means to address the as-yet-unanswered key questions related to the development of arthritis.
Kyburz
Diego
D
Department of Rheumatology, University Hospital of Zurich, Gloriastrasse 25, 8091, Zurich, Switzerland.
Corr
Maripat
M
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003182:Complement C5 / Q000172:deficiency / Q000502:physiology; D004195:Disease Models, Animal; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000276:immunology; D007596:Joints / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D003182:Complement C5; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D005956:Glucose-6-Phosphate Isomerase