Characterization of a novel and spontaneous mouse model of inflammatory arthritis

Arthritis is a heterogeneous disease comprising a group of inflammatory and non-inflammatory conditions that can cause pain, stiffness and swelling in the joints. Mouse models of rheumatoid arthritis (RA) have been critical for identifying genetic and cellular mechanisms of RA and several new mouse models have been produced. Various methods have been applied to induce experimental models of arthritis in animals that would provide important insights into the etiopathogenetic mechanisms of human RA. Adipue and colleagues recently discovered that mice in their breeding colony spontaneously developed inflamed joints reminiscent of RA and may, therefore, have found a new model to examine pathogenic mechanisms and test new treatments for this human inflammatory disease.


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).

Characterization of a novel and spontaneous mouse model of infl ammatory arthritis
Adipue and colleagues [1] describe a new strain of mouse that spontaneously develops a chronic infl ammatory, possibly autoimmune, arthritis that shares many simi larities with human RA and other mouse models of arthritis. Th e authors point out that arthritis incidence in IIJ mice also displays the sex bias common to many complex autoimmune diseases such as RA, multiple sclerosis, and systemic lupus erythematosus [8]. Th e sex bias appears to be specifi c for the arthritis phenotype since the incidence of typhlocolitis was similar between male and female IIJ mice. As most models reach 100% incidence in both sexes, no other spontaneous mouse model of arthritis has displayed such a sex bias, although more severe arthritis

Abstract
Arthritis is a heterogeneous disease comprising a group of infl ammatory and non-infl ammatory conditions that can cause pain, stiff ness and swelling in the joints. Mouse models of rheumatoid arthritis (RA) have been critical for identifying genetic and cellular mechanisms of RA and several new mouse models have been produced. Various methods have been applied to induce experimental models of arthritis in animals that would provide important insights into the etiopathogenetic mechanisms of human RA. Adipue and colleagues recently discovered that mice in their breeding colony spontaneously developed infl amed joints reminiscent of RA and may, therefore, have found a new model to examine pathogenic mechanisms and test new treatments for this human infl ammatory disease. in females has been reported for both the SKG [7] and gp130Y759F models [9]. A female bias in incidence was also observed in collagen-induced arthritis in humanized HLA-DR4-transgenic mice [10] and was attributed to both hyperactive B cells and HLA-DR4 restricted antigen presentation in female mice and increased numbers of T and B regulatory cells in male mice [11]. In particular, Adipue and colleagues emphasize that the histopathology in IIJ mice is similar to that described in previously published mouse models of autoimmune arthritis [7,9]. In addition, the predominantly neutrophilic and lymphocytic infi ltration into the infl amed IIJ joints parallels the large numbers of neutrophils and T cells present in the infl amed synovial fl uid of RA patients [12]. Finally, the IIJ mice also share serological similarities with RA and some other mouse models.

Conclusion
Adipue and colleagues have identifi ed the IIJ strain as a new murine model of infl ammatory, possibly autoimmune, arthritis. Th e IIJ strain is similar both histologically and serologically to RA and other murine models of auto immune arthritis. Moreover, the increased incidence of arthritis in female IIJ mice makes it a potentially impor tant model to study the underlying causes of sex bias in autoimmunity.

Competing interests
The author declares that they have no competing interests.