**6. Future prospect**

study the role of antibodies in the development of RA [66]. This model alone demonstrates that a specific molecule or antibody is not required to generate arthritis. The receptor of the T cells of the KRN strain recognizes the GPI and, on the other hand, the MHC [99]. This immune recognition of G6PI gives rise to autoantibodies to the isomerase which, when purified, can transfer disease. The relevance of this reactivity to the etiology of RA is unclear. Recognition of G6PI is first obtained by antibodies, and subsequently these can be transferred, although the

The transgenic T-cell receptor of the krn strain was originally generated to recognize a bovinetype antigen; its discovery was totally serendipity. Different authors have performed different series of studies to define the mechanism of action, the effector phases, as well as the evalua-

On the other hand, immunization with G6PI induces an inflammatory arthritis that is dependent on T cells in mice that have not been studied, generating clues about the knowledge and

In this model, arthritis is produced by transfer of serum antibodies from a previous arthritis model; mice are genetically modified to develop RA when it is induced. The targets in this model are cytokines and chemokines. The absence of these molecules is analyzed to verify if they generate protection or induction of RA and additional information such as the signaling pathway that it alters. The TRANCE/RANKL factor was one of the most used for evaluation of the NF-kB pathway with TNF [101]. The phenotypic characteristics of the major animal

**Figure 3.** Phenotypic characteristics of animal models. There are different strains of mice and rats used as models for the evaluation of RA; among them the most representative strains are Lewis, DBA 1/J, C57BL/6, and K BxN, which respond

relevancy of this discovery does not really generate knowledge toward RA.

tion of cells involved in this animal model of RA [99].

272 Experimental Animal Models of Human Diseases - An Effective Therapeutic Strategy

use of such a model [100].

models are shown in **Figure 3**.

to different genotypic and phenotypic characteristics.

Animal models, as we have already commented, still are the strongest link to evaluate therapeutic compounds, at least in autoimmune diseases, such as rheumatoid arthritis. In general, each model provides different information about the disease, and it is suggested that for more reliable results, the evaluated compounds have been tested in two different models to have a little more certainty of the effects generated by the molecules that are determined in each experiment.

Efforts are currently directed to find a model that can more accurately reproduce the symptoms and signs of RA taking the security of continuing to obtain reliable results. Another strategy is that the route of administration is as aggressive and invasive as possible but reproduces precise results, so other routes are being evaluated such as systemic to thus discontinue intra-articular injection.

These studies are carried out with the aim of using as few animals as possible and, in turn, with the least suffering, due to the techniques to inoculate the therapeutic agent to be evaluated, in addition to the fact that the population decline does not interfere in the test results.
