THE NOD MOUSE: A Model of Immune Dysregulation
Abstract
Autoimmunity is a complex process that likely results from the summation of multiple defective tolerance mechanisms. The NOD mouse strain is an excellent model of autoimmune disease and an important tool for dissecting tolerance mechanisms. The strength of this mouse strain is that it develops spontaneous autoimmune diabetes, which shares many similarities to autoimmune or type 1a diabetes (T1D) in human subjects, including the presence of pancreas-specific autoantibodies, autoreactive CD4+ and CD8+ T cells, and genetic linkage to disease syntenic to that found in humans. During the past ten years, investigators have used a wide variety of tools to study these mice, including immunological reagents and transgenic and knockout strains; these tools have tremendously enhanced the study of the fundamental disease mechanisms. In addition, investigators have recently developed a number of therapeutic interventions in this animal model that have now been translated into human therapies. In this review, we summarize many of the important features of disease development and progression in the NOD strain, emphasizing the role of central and peripheral tolerance mechanisms that affect diabetes in these mice. The information gained from this highly relevant model of human disease will lead to potential therapies that may alter the development of the disease and its progression in patients with T1D.
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β-cell-specific CD8 T cells in NOD mice are primed in the pancreatic draining lymph node (pLN) before they infiltrate the pancreas.
“β-cell-specific CD8 T cells in NOD mice are primed in the pancreatic draining lymph node (pLN) before they infiltrate the pancreas6,11.”
From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [6]
CD8 T cells recognizing the β-cell protein IGRP represent a major pathogenic population in mice and humans.
“CD8 T cells recognizing the β-cell protein islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) represent a major pathogenic population in mice and humans6,8,10.”
From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [6]
The non-obese diabetic (NOD) mouse model is a clinically relevant model of T1D and shares many features with the human disease, including spontaneous CD4 and CD8 T cell responses to many of the same β-cell antigens.
“The non-obese diabetic (NOD) mouse model is a clinically relevant model of T1D6,7 and shares many features with the human disease, including spontaneous CD4 and CD8 T cell responses to many of the same β-cell antigens6–9.”
From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [6]
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- Authors
- Anderson, M. S., & Bluestone, J. A.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2005-04-01
- Volume
- 23
- Issue
- 1
- Pages
- 447-485
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- OpenAlex
- W2082137006
- Cited by
- 1,113
- References
- 6
- Citations by year
- 2026: 20 · 2025: 27 · 2024: 41 · 2023: 43 · 2022: 40 · 2021: 38 · 2020: 33 · 2019: 41 · 2018: 46 · 2017: 52 · 2016: 47 · 2015: 69 · 2014: 61 · 2013: 74 · 2012: 85
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01 AI50834, R01AI050834, U19AI056388, U19 AI56388)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK059958, P30-DK-63720, P30DK063720)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- NOD mice, type 1 diabetes, autoimmune disease, immune tolerance, central tolerance, peripheral tolerance, autoantibodies, autoreactive T cells, disease progression, therapeutic interventions
- MeSH terms
- Animals, Cell Differentiation, Diabetes Mellitus, Type 1, Disease Models, Animal, Immune Tolerance, Lymphocyte Activation, T-Lymphocyte Subsets, Mice, Inbred NOD, Models, Immunological, Mice
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