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History
Non-obese diabetic (NOD) mice exhibit a susceptibility to spontaneous development of automimmune insulin dependent diabetes mellitus (IDDM)[2]. The NOD strain and related strains were developed at Shionogi Research Laboratories in Aburahi, Japan by Makino and colleagues and first reported in 1980 [3]. The group developed the NOD strain by selecting cataract-prone strains. The strain was then established by inbreeding.
Characteristics
Diabetes develops in NOD mice as a result of insulitis, a leukocytic infiltrate of the pancreatic islets. 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. The incidence of spontaneous diabetes in the NOD mouse is 60-80% in females and 20-30% in males. Onset of diabetes will also vary between males and females: commonly the onset is delayed in males by several weeks.
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 effect development of diabetes in the mice. Interestingly, the incidence of disease is much higher if the mice are maintained in a relatively germ-free environment.
NOD mice are also susceptible to developing other autoimmune syndromes, including autoimmunine sialitis, autoimmune thyroiditis, autoimmune peripheral polyneuropathy, a systemic lupus erythematosus-like disease that develops if mice are exposed to killed mycobacterium, and prostatitis.
NOD mice show a defect in the ld33 locus which is 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. (Tang Q, Bluestone JA et al, Immunity 28, 687-697, May 2008)
References
- ^ "Non-Obese Diabetic (NOD) Mouse BAC Library". National Institute of Allergy and Infectious Diseases. Retrieved on 2006-05-15.
- ^ Kikutani H, Makino S (1992). "The murine autoimmune diabetes model: NOD and related strains". Adv. Immunol. 51: 285–322. PMID 1323922.
- ^ Makino S, Kunimoto K, Muraoka Y, Mizushima Y, Katagiri K, Tochino Y (1980). "Breeding of a non-obese, diabetic strain of mice". Jikken Dobutsu 29 (1): 1–13. PMID 6995140.
