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Editorial

Characterization of a novel and spontaneous mouse model of inflammatory arthritis

Salvatore Cuzzocrea

Author Affiliations

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario, Via C. Valeria, Gazzi, 98100 Messina, Italy

Arthritis Research & Therapy 2011, 13:126  doi:10.1186/ar3434


See related research by Adipue et al., http://arthritis-research.com/content/13/4/R114

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/13/5/126


Published:16 September 2011

© 2011 BioMed Central Ltd

Abstract

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 inflamed joints) mouse strain, a new murine model of inflammatory, 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 inflammatory disorder characterized by synovitis and severe joint destruction. The pathogenesis of RA is a complex process, involving synovial cell proliferation and fibrosis, 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), thymocytes (C3H/He), mycoplasma (CBA), or a high fat diet (C57BL). Spontaneous models can be grouped according to their origin: development of autoimmune-prone strains by selective mixing of previously existing inbred strains (for example, the MRL/lpr strain [3]); targeted gene manipulation (for example, the TCR trans-genic K/BxN model [4], TNF-α overexpression models [5], the IL-1Ra knock-out model [6], and the gp130Y759F-induced mutant); and identification of spontaneous mutants from breeding colonies (for example, SKG mice with a point mutation in Zap-70 [7]).

Table 1. Animal models of arthritis

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 different between different strains of mice, even if the same induction protocol is employed, and some of the strains are even selected because of their susceptibility to auto-immunity. 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 inflammatory processes and the pathways involved in cartilage and bone erosion and, therefore, have helped identify new therapeutic targets (Table 2).

Table 2. Drugs used to treat arthritis

Characterization of a novel and spontaneous mouse model of inflammatory arthritis

Adipue and colleagues [1] describe a new strain of mouse that spontaneously develops a chronic inflammatory, possibly autoimmune, arthritis that shares many similarities with human RA and other mouse models of arthritis. The 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]. The sex bias appears to be specific 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 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 infiltration into the inflamed IIJ joints parallels the large numbers of neutrophils and T cells present in the inflamed synovial fluid of RA patients [12]. Finally, the IIJ mice also share serological similarities with RA and some other mouse models.

Conclusion

Adipue and colleagues have identified the IIJ strain as a new murine model of inflammatory, possibly autoimmune, arthritis. The IIJ strain is similar both histologically and serologically to RA and other murine models of autoimmune arthritis. Moreover, the increased incidence of arthritis in female IIJ mice makes it a potentially important model to study the underlying causes of sex bias in autoimmunity.

Abbreviations

IIJ: inherited inflamed joint; IL: interleukin; RA: rheumatoid arthritis.

Competing interests

The author declares that they have no competing interests.

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