Mouse model of rheumatoid arthritis

Adipue and colleagues [1] have characterized the novel IIJ (inherited infl amed joints) mouse strain, a new murine model of infl ammatory, possibly autoimmune, arthritis that is similar both histologically and serologically to human rheumatoid arthritis (RA) and other murine models of autoimmune arthritis [1]. RA is a chronic and progressive infl ammatory disorder characterized by synovitis and severe joint destruction. Th e pathogenesis of RA is a complex process, involving synovial cell proliferation and fi brosis, pannus formation, and cartilage and bone erosion [2]. Rodent models of RA have been used extensively to evaluate potential new therapeutic agents. Arthritis in the mouse can be induced, can occur spontaneously in some inbred strains, or can result from single gene mutations (Table 1). Induced murine arthritis models include immunization with type II collagen (DBA/1LacJ), or treatment with pristane (BALB/c), thymo cytes (C3H/He), mycoplasma (CBA), or a high fat diet (C57BL). Spontaneous models can be grouped according to their origin: development of autoimmuneprone strains by selective mixing of previously existing inbred strains (for example, the MRL/lpr strain [3]); targeted gene manipulation (for example, the TCR transgenic K/BxN model [4], TNF-α overexpression models [5], the IL-1Ra knock-out model [6], and the gp130Y759Finduced mutant); and identifi cation of spontaneous mutants from breeding colonies (for example, SKG mice with a point mutation in Zap-70 [7]). Despite the existence of all of these models, it is well known that no animal model represents RA in its entirety. In addition, clinical manifestations are diff erent between diff erent strains of mice, even if the same induction protocol is employed, and some of the strains are even selected because of their susceptibility to autoimmunity. Even though it is improbable that a single animal model could assume and reproduce human disease in its entirety and consistently, animal models have allowed us to understand common principles of the induction and persistence of infl ammatory processes and the pathways involved in cartilage and bone erosion and, therefore, have helped identify new therapeutic targets (Table 2).