The pathogenesis of autoimmunity in New Zealand mice

Andrea Borchers, Aftab A. Ansari, Tom Hsu, Dwight H. Kono, M. Eric Gershwin

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Objective: New Zealand mice were the first spontaneous animal model of human systemic lupus erythematosus (SLE). Since their initial discovery in 1959, studies of these mice have provided insights into the immunopathogenesis and genetics of lupus and have had a substantial impact on our understanding of autoimmunity. Methods: We extensively reviewed published data for the past 40 years, including work in cellular immunology and molecular biology, to provide new information on the role of lymphoid subpopulations, cytokines, costimulatory molecules, apoptosis, and genetic susceptibility in the natural history of immunopathology in murine lupus. Results: Genetic factors constitute the most important contribution to autoimmunity in New Zealand mice, and specific major susceptibility loci have been described. In addition, there is evidence for a pluripotent stem cell defect, which has implications for developmental and functional defects of T and B cells. The end result of these defects is a breakdown of self-tolerance and production of autoantibodies. Further studies will undoubtedly shape our understanding of this murine model and provide the basis for novel diagnostic and therapeutic approaches in humans. Conclusions: The advent of molecular biology, including the use of monoclonal antibody therapy in New Zealand mice, has been instrumental in our understanding of the loss of self- tolerance in SLE. Finally, identification of genetic susceptibility loci in the murine system has also led to important comparable studies in humans with SLE. Relevance: The observations in New Zealand mice are of particular importance to systemic lupus erythematosus (SLE). Copyright (C) 2000 by W.B. Saunders Company.

Original languageEnglish (US)
Pages (from-to)385-399
Number of pages15
JournalSeminars in Arthritis and Rheumatism
Volume29
Issue number6
StatePublished - 2000

Keywords

  • Autoantibodies
  • Genetics of autoimmunity
  • Immune regulation
  • Murine lupus

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Orthopedics and Sports Medicine
  • Rheumatology

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    Borchers, A., Ansari, A. A., Hsu, T., Kono, D. H., & Gershwin, M. E. (2000). The pathogenesis of autoimmunity in New Zealand mice. Seminars in Arthritis and Rheumatism, 29(6), 385-399.