ABSTRACT
Animal models have been helpful in better understanding the biology of both hematopoietic stem cells (HSC) and autoimmunity. Autoimmunity is caused by a complex interplay of genetic and environmental factors. Spontaneous animal models of autoimmunity result from germ-line mutations; these include the lpr/lpr mouse as a model for arthritis and vasculitis, 1 the NOD (nonobese diabetic) mouse for diabetes, and the NZB/W mouse for systemic lupus erythematosus. 2 Although studies of murine susceptibility genes are likely to provide insights into the genetic mechanisms involved in the human predisposition to autoimmunity, these models differ significantly from most cases of human autoimmune disease. Spontaneous animal models with germ-line mutations virtually always develop autoimmunity, while only a fraction of individuals who harbor susceptibility genes develop autoimmunity; there are rare exceptions to this, such as patients with the autoimmune lymphoproliferative syndrome (ALPS), who, like lpr/lpr mice, inherit loss-of-function mutations of the Fas gene (refer to Chapter 17). 3 , 4 Induced animal models of autoimmunity focus on the role of environmental factors in the development of autoimmunity. 2 These animal models more closely approximate most cases of human autoimmunity, and have the advantage over spontaneous models in that the onset and progression of the disease can be controlled (refer to Chapters 29 and 30).
