The SKG model of spondyloarthritis

Abstract

Animal models of human diseases are used to study a broad array of autoimmune disorders including spondyloarthritis (SpA). Various animal models, either genetically engineered, spontaneous or induced, have been described to address the fundamental pathological features of human SpA. With the advent of novel techniques for manipulations in animal models, it has become possible to delineate critical pathways involved in SpA disease mechanisms and to develop novel therapeutics. In this chapter, we discuss animal models to study the fundamental characteristics of human SpA. None of the animal models developed exactly mimics human diseases, but some of the models closely resemble the group of human SpA diseases. The SKG mouse, in particular, harbours a point mutation in the ZAP-70 gene yielding reduced T-cell receptor (TCR) signalling, develops multi-organ inflammation under microbial influence, mimics human SpA disease pathogenesis and is a promising tool for designing new therapeutics against SpA. We describe the contribution of animal models to the earliest known disease mechanisms, including how attenuated T cell signalling contributes to disease pathogenesis as a result of genetic or environmental predisposition. We also discuss recent advances in the understanding of key cytokines that drive SpA pathophysiology and the crosstalk of gut microbiota with host genetic determinants of immune function and finally the potential future prospects to study these animal models to translate our knowledge of pathogenesis into clinical practice.

Keywords: Animal model; Gut microbiota; SKG; Spondyloarthritis; T cell; ZAP-70.