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Abstract

MRL/1 mice spontaneously develop a hindlimb arthropathy, as well as a number of immunologic abnormalities, including circulating rheumatoid factors. Although previous studies have suggested that this arthropathy is primarily an inflammatory process, we performed a comprehensive histomorphologic study which indicated that inflammation is a late manifestation of MRL/1 arthritis. The pathologic changes that occur in the joints of these mice can be divided into 3 stages. The first stage develops between the ages of 7 and 13 weeks and consists of synovial cell proliferation in the joint recesses. The second stage is characterized by continued proliferation of synovial cells which take on an appearance similar to that of transformed mesenchymal cells. The earliest destructive changes occur in the second stage and include marginal erosions, followed soon after by progressive destruction of articular and meniscal cartilage. The final stage is characterized by a diminution of synovial cell proliferation, extensive cartilage destruction, formation of scar tissue and fibrocartilage, and a very moderate infiltration of the synovial stroma by mononuclear and polymorphonuclear inflammatory cells. Throughout the disease progression there is a striking dissociation between inflammatory cell infiltration or exudation and tissue destruction. The histomorphologic similarities between human rheumatoid synovitis and the arthritis of MRL/1 mice, as well as the presence of rheumatoid factors, make this mouse strain an excellent model for studying human rheumatoid arthritis.