NOD.H-2h4 mice: an important and underutilized animal model of autoimmune thyroiditis and Sjogren's syndrome

Adv Immunol. 2015;126:1-43. doi: 10.1016/ Epub 2015 Feb 7.


NOD.H-2h4 mice express the K haplotype on the NOD genetic background. They spontaneously develop thyroiditis and Sjogren's syndrome, but they do not develop diabetes. Although autoimmune thyroid diseases and Sjogren's syndrome are highly prevalent autoimmune diseases in humans, there has been relatively little emphasis on the use of animal models of these diseases for understanding basic mechanisms involved in development and therapy of chronic organ-specific autoimmune diseases. The goal of this review is to highlight some of the advantages of NOD.H-2h4 mice for studying basic mechanisms involved in development of autoimmunity. NOD.H-2h4 mice are one of relatively few animal models that develop organ-specific autoimmune diseases spontaneously, i.e., without a requirement for immunization with antigen and adjuvant, and in both sexes in a relatively short period of time. Thyroiditis and Sjogren's syndrome in NOD.H-2h4 mice are chronic autoimmune diseases that develop relatively early in life and persist for the life of the animal. Because the animals do not become clinically ill, the NOD.H-2h4 mouse provides an excellent model to test therapeutic protocols over a long period of time. The availability of several mutant mice on this background provides a means to address the impact of particular cells and molecules on the autoimmune diseases. Moreover, to our knowledge, this is the only animal model in which the presence or absence of a single cytokine, IFN-γ, is sufficient to completely inhibit one autoimmune thyroid disease, with a completely distinct autoimmune thyroid disease developing when it is absent.

Keywords: Autoimmunity; Mouse models; Sjogren's syndrome; Thyroiditis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoimmunity
  • Disease Models, Animal*
  • Female
  • Humans
  • Interferon-gamma / immunology
  • Lymphocytes / immunology
  • Male
  • Mice
  • Mice, Inbred NOD / immunology*
  • Mice, Knockout
  • Sjogren's Syndrome / immunology*
  • Thyroiditis, Autoimmune / immunology*


  • Autoantibodies
  • Interferon-gamma