Autoimmune Disease Induced Animal Models

W J Penhale, Institute of Molecular Genetics and Animal Disease, School of Veterinary Studies, Murdoch University, Murdoch, Australia

Copyright © 1998 Elsevier Ltd. All Rights Reserved.

The first indication that the immune system could be experimentally provoked into dangerous self reactivity stems from the early 1930s when Rivers and his colleagues induced encephalomyelitis in monkeys by the injection of brain material. Some 20 years later, Voisin and coworkers made the, quite literally, seminal observation that testicular lesions could be similarly induced by testicular extracts including spermatozoa. Although these studies provided the prototype animal models of autoimmune diseases, the foundations of experimental autoimmunity were not truly laid until Rose and Witebsky demonstrated in a series of classical studies that both antibodies to thyroid constituents and thyroiditis could be induced by immunizing rabbits with thyroid extracts in Freund's complete adjuvant. Since then, many experimental models have been developed in a broad range of animal species and, consequently, the 1975 prediction of Wick - that autoimmune disease may be induced in any organ provided the investigator tries hard enough - seems ever more likely. In addition, new experimental approaches not involving specific immunization have been introduced and these have widened the scope and range of disease models now available for study. These later models have opened alternative avenues for investigation and, in consequence, new conceptual insights into the autoimmune process have been made.

As a group, induced models may be defined as those in which an autoimmune process is superimposed on otherwise normal, unaffected animals by a variety of treatments or manipulations. They contrast with the spontaneous models where disease occurs without intervention and is largely, although not entirely, determined by genetic composition. In consequence, whilst spontaneous models are limited to a particular genome, induced models are well suited to the investigation of genetic influences by their imposition on inbred strains of differing genetic constitution. They also have the particular advantages that normal syngeneic animals are available for parallel control studies, as recipients in adoptive transfer experiments, and also for the provision of cells for reconstitution studies in depleted animals.

The extensive range of induced animal models that is currently available has resulted from an expanding variety of induction strategies and can be con veniently grouped on this basis. Since the methods employed often reflect fundamental differences in both the triggering and pathogenic mechanisms, each type provides its own insight into autoimmune pathogenesis and has particular advantages for research in selected areas. Despite these widely differing inductive procedures, however, it is likely that the terminal pathogenic pathways coincide when a common organ is involved. These aspects will be discussed in the following sections which briefly review the various models currently available.

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