NOD mice
Non-obese diabetic or NOD mice, like the Biobreeding rat, are used as an animal model for type 1 diabetes.[1] Diabetes develops in NOD mice as a result of insulitis, a leukocytic infiltrate of the pancreatic islets.[2] Onset of diabetes is associated with a moderate glycosuria and a non-fasting hyperglycaemia. It is recommended to monitor for development of glycosuria from 10 weeks of age; this can be carried out using urine glucose dipsticks. NOD mice will develop spontaneous diabetes when left in a sterile environment. [3] The incidence of spontaneous diabetes in the NOD mouse is 60-80% in females and 20-30% in males. Onset of diabetes also varies between males and females: commonly, onset is delayed in males by several weeks.
History
Non-obese diabetic (NOD) mice exhibit a susceptibility to spontaneous development of autoimmune insulin dependent diabetes mellitus (IDDM).[4] The NOD strain and related strains were developed at Shionogi Research Laboratories in Aburahi, Japan by Makino and colleagues and first reported in 1980.[5] The group developed the NOD strain by an outbreeding of the cataract-prone strain from JcI:ICR mice. [6]
Susceptibility
The susceptibility to IDDM is polygenic and environment exerts a strong effect on gene penetrances. Environment including housing conditions, health status, and diet all affect development of diabetes in the mice. For instance, NOD mice maintained in different laboratories can have different levels of incidence. Interestingly, the incidence of disease is linked to Microbiome.[7]
NOD mice are also susceptible to developing other autoimmune syndromes, including autoimmunine sialitis, autoimmune thyroiditis, autoimmune peripheral polyneuropathy etc. Diabetes in these mice can be prevented by a single injection of mycobacterial adjuvants such as complete Freund's adjuvant (FCA) or Bacille de Calmette et Guérin or BCG vaccine.[8][9]
Identifying IDDM susceptibility loci
Genetic Loci associated with susceptibility to IDDM have been identified in the NOD mouse strain through the development of congenic mouse strains, which have identified several insulin dependent diabetes (Idd) loci. The most important is idd1which is the major histocompatibilty complex class II loci I-Ag7.[10]
NOD mice have polymorphisms in the Idd3 locus which are linked to IL-2 production. IL-2 promotes either immunity or tolerance in a concentration dependent fashion by acting on T helper cells, CTL and NK cells. Low amounts of IL-2 may be needed to promote survival of Treg in mice. Loss of IL-2 can thereby contribute to the development of autoimmunity in NOD mice.[11]
NOD mice have a mutation in exon 2 of the CTLA-4 gene, which causes it to be spliced incorrectly. CTLA-4 plays a major role in suppressing the T-cell immune response. Without the proper functioning of CTLA-4 T-cells attack the insulin producing cells. This results in Type 1 Diabetes.[12]
References
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- ↑ Delovitch TL, Singh B. The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity. 1997; 7:727-38. PMID 9430219
- ↑ Eisenbarth, GS. Type 1 Diabetes: Molecular Cellular and Clinical Immunology. 2004; 552
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- ↑ Sadelain MW, Qin HY, Lauzon J, Singh B. Prevention of type I diabetes in NOD mice by adjuvant immunotherapy. Diabetes. 1990;39:583-9. PMID 2139617
- ↑ Qin HY, Sadelain MW, Hitchon C, Lauzon J, Singh B. Complete Freund's adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice. J Immunol. 1993;150:2072-80. PMID 8436836
- ↑ Serreze DV, Leiter EH. Genetic and pathogenic basis of autoimmune diabetes in NOD mice. Curr Opin Immunol. 1994; 6:900-6. PMID 7710714
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
