Lessons on autoimmune diabetes from animal models
- PMID: 16689681
- DOI: 10.1042/CS20050330
Lessons on autoimmune diabetes from animal models
Abstract
T1DM (Type I diabetes mellitus) results from selective destruction of the insulin-producing beta-cells of the pancreas by the immune system, and is characterized by hyperglycaemia and vascular complications arising from suboptimal control of blood glucose levels. The discovery of animal models of T1DM in the late 1970s and early 1980s, particularly the NOD (non-obese diabetic) mouse and the BB (BioBreeding) diabetes-prone rat, had a fundamental impact on our ability to understand the genetics, aetiology and pathogenesis of this disease. NOD and BB diabetes-prone rats spontaneously develop a form of diabetes that closely resembles the human counterpart. Early studies of these animals quickly led to the realization that T1DM is caused by autoreactive T-lymphocytes and revealed that the development of T1DM is controlled by numerous polymorphic genetic elements that are scattered throughout the genome. The development of transgenic and gene-targeting technologies during the 1980s allowed the generation of models of T1DM of reduced genetic and pathogenic complexity, and a more detailed understanding of the immunogenetics of T1DM. In this review, we summarize the contribution of studies in animal models of T1DM to our current understanding of four fundamental aspects of T1DM: (i) the nature of genetic elements affording T1DM susceptibility or resistance; (ii) the mechanisms underlying the development and recruitment of pathogenic autoreactive T-cells; (iii) the identity of islet antigens that contribute to the initiation and/or progression of islet inflammation and beta-cell destruction; and (iv) the design of avenues for therapeutic intervention that are rooted in the knowledge gained from studies of animal models. Development of new animal models will ensure continued progress in these four areas.
Similar articles
-
Autoimmune disorders in diabetes.Adv Nephrol Necker Hosp. 1986;15:281-305. Adv Nephrol Necker Hosp. 1986. PMID: 3082114 Review.
-
Dynamic interaction between T cell-mediated beta-cell damage and beta-cell repair in the run up to autoimmune diabetes of the NOD mouse.Physiol Genomics. 2005 Apr 14;21(2):201-11. doi: 10.1152/physiolgenomics.00173.2004. Epub 2005 Jan 25. Physiol Genomics. 2005. PMID: 15671250
-
The thymus-dependent immune system in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus. Animal model and human studies.Dan Med Bull. 1985 Jun;32(3):139-51. Dan Med Bull. 1985. PMID: 3160550 Review.
-
CD8+ T cells in type 1 diabetes.Adv Immunol. 2008;100:79-124. doi: 10.1016/S0065-2776(08)00804-3. Adv Immunol. 2008. PMID: 19111164 Review.
-
Identification of QTLs that modify peripheral neuropathy in NOD.H2b-Pdcd1-/- mice.Int Immunol. 2009 May;21(5):499-509. doi: 10.1093/intimm/dxp020. Epub 2009 Mar 4. Int Immunol. 2009. PMID: 19261693
Cited by
-
Type 2 diabetes mellitus--an autoimmune disease?Nat Rev Endocrinol. 2013 Dec;9(12):750-5. doi: 10.1038/nrendo.2013.131. Epub 2013 Jul 9. Nat Rev Endocrinol. 2013. PMID: 23835371 Review.
-
Animal Models of Diabetes-Associated Renal Injury.J Diabetes Res. 2020 May 20;2020:9416419. doi: 10.1155/2020/9416419. eCollection 2020. J Diabetes Res. 2020. PMID: 32566684 Free PMC article. Review.
-
Understanding type 1 diabetes through genetics: advances and prospects.Nat Rev Genet. 2011 Oct 18;12(11):781-92. doi: 10.1038/nrg3069. Nat Rev Genet. 2011. PMID: 22005987 Review.
-
2α-Methyl-19-nor-(20S)-1,25-dihydroxyvitamin D(3) protects the insulin 2 knockout non-obese diabetic mouse from developing type 1 diabetes without hypercalcaemia.Clin Exp Immunol. 2011 Dec;166(3):325-32. doi: 10.1111/j.1365-2249.2011.04481.x. Clin Exp Immunol. 2011. PMID: 22059989 Free PMC article.
-
Pathogenesis of Type 1 Diabetes Mellitus and Rodent Experimental Models.Acta Naturae. 2018 Jan-Mar;10(1):24-33. Acta Naturae. 2018. PMID: 29713516 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical