Experimental Models of Lupus Erythematosus

Abstract

without appropriate animal models, although no single animal model perfectly mimics a human disease. Animal models are commonly used to study the genetic, environmental, and pathogenic aspects of autoimmune diseases. Regarding experimental autoimmune diseases, these models can be divided into several broad groups: (a) inbred mice that spontaneously develop a disease similar to human systemic lupus erythematosus (SLE); (b) chronic graft-vs-host diseases induced in F1 hybrid mice injected with lymphoid parental cells; (c) ultraviolet (UV) light-irradiated mice immunized with some components of DNA; (d) immunodeficient mice such as severe combined immunodeficient (SCID) mice and nude mice inoculated or engrafted with immunocompetent cells or tissues; and (e) gene-manipulated mice such as transgenic or knockout mice. There are many inbred strains of SLE-prone mice, including New Zealand Black (NZB), F1 hybrids of NZB × New Zealand White (NZW) (B/W F1), MRL/Mp-lpr/lpr (MRL/lpr), and BXSB mice. The postulated etiologic factors of these murine diseases include retroviruses, thymic abnormalities, antithymocyte antibodies, polyclonal Bcell activation, an impaired balance of T-cell interaction, and abnormalities of phagocytic cells (Andrews et al. 1978). Such abnormalities described in SLE now span the spectrum from cellular immunology to immunoglobulin idiotypes, cytokines, apoptosis, DNA repair, and endogenous retroviruses (Steinberg 1995). Immunologic tolerance is now revisited to study the systemic and organ-specific autoimmune diseases (Nishimura and Honjo 2001, Shimizu et al. 2002). Based on these trends, several new and important studies on the pathogenesis of lupus have been reported in the field of internal organ biology, including the kidney, lung, and salivary glands. In this review, based on historical review, we focus on skin lesions from the well-studied MRL/lpr and B/W F1 mice and discuss how SLE-prone mice can contribute to a better understanding of the pathogenesis of cutaneous LE (CLE).