NOD mice
Encyclopedia
Non-obese diabetic or NOD mice
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...

, like the Biobreeding rat
Biobreeding rat
Biobreeding rat also known as the BB or BBDP rat is an inbred laboratory rat strain that spontaneously develops autoimmune Type 1 Diabetes. Like the NOD mice, BB rats are used as an animal model for Type 1 diabetes...

, are used as an animal model
Model organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...

 for type 1 diabetes.

History

Non-obese diabetic (NOD) mice exhibit a susceptibility to spontaneous development of autoimmune insulin dependent diabetes mellitus (IDDM). The NOD strain and related strains were developed at Shionogi Research Laboratories in Aburahi, Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

 by Makino and colleagues and first reported in 1980 . 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
Glycosuria
Glycosuria or glucosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reclaim all of the filtered glucose back into the bloodstream. Glycosuria is nearly always caused by elevated blood glucose levels, most commonly due to...

 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 also varies between males and females: commonly, onset is delayed in males by several weeks.

Susceptibility

The susceptibility to IDDM is polygenic and environment exerts a strong effect on gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 penetrances. Environment including housing conditions, health status, and diet all effect 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 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
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...

-like disease that develops if mice are exposed to killed mycobacterium, and prostatitis.

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.

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.
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