Autoimmunity is considered to be a complex process resulting from defective tolerance mechanisms summation; the NOD mouse is strain serves as an important autoimmune disease model and an excellent tool for the tolerance mechanisms dissecting. It is necessary to underline the fact that the strength of this strain is concentrated on its development of spontaneous autoimmune diabetes sharing its similarities to T1D (type 1a diabetes); the nonobese diabetic mouse is used in IDDM (insulin-dependent diabetes mellitus) developing a T-cell-mediated disease, which is characterized through considerable infiltrations of pancreatic islets. Numerous experiments have demonstrated the fact that the NOD mouse crossing with a scurfy mouse model leads to the generation of NOD/Foxp3 mouse, suffering from inflammatory disorders and severe lymphoproliferation and dying by 3 weeks.
It is necessary to underline the fact that the NOD mouse model has a strong genetic component mapping to the genome histocompatibility complex. Recent experiments have shown certain proteasome defects in lymphocytes of the NOD; these defects are resulted from the insufficient number of LMP2 subunits. It should be noted that the proteasome defect of the NOD mouse model leads to defective production and activation of NF-kB factor playing a significant role in inflammatory responses and apoptosis prevention being induced through the tumor necrosis factor alpha. Phenotypically, the evidence of the defect can be evident by impaired NF-k protein degradation and proteolytic processing. (Chen, and Benoist, 2005)
Type 1 diabetes in NOD mouse is considered to be the result of the destruction of T-cell-mediated autoimmune of insulin-producing pancreatic beta-cells. It is necessary to stress that multiple susceptibility genes are the part of type 1 diabetes; the combinations of MHC (histocompatibility complex) genes create the primary component of the NOD mice type1 diabetes susceptibility. (Goudy, and Song, 2001)
The scurfy mouse is considered to be the phenotypic and genetic equivalent to the single-gene autoimmune disease of human beings, characterized by X-linked (IPEX), immune dysregulation, enteropathy, polyendocrinopathy. Phenotypes being associated with this mouse cover scaly, running, crusty skin on the ears, squinted eyes, dermal thickening and genital papilla swelling. The crossbreeding of the mice leads to the development of severe immune disease; it can be explained by the fact that this mouse develops disease resulting from defective form of T cell tolerance. After 14 days of the age, the defective NOD/Foxp3 mouse started to develop occasional peri-insulitis and exocrine pancreatitis; by 3 weeks of age the crossbred deficient mouse suffers inflammatory infiltration and lymphoproliferation in skin, lungs, stomach, liver, colon, and fat, leading to the death. (Murphy, Travers, and Janeway, 2008)
The experimental method for the prolonging of mice life is based on the inducing the tolerance to the CC57BR mice through injections of C heart killed. The vaccine was provided after the 3 days of life for 2 weeks. This method was aimed at producing the tolerance, demonstrating the death of 30% of animals. This considerably raised the chance of life prolonging based on antigen injection of control and experimental mice NOD/Foxp3. The second method of life prolonging is based on the attempts to produce immunological tolerance after the process of repeated injections to disrupted spleen cells. This demonstrated vivid improvements of the skin and lungs condition. (Jaeckel, and Klein, 2003)
References
Cnen, Y, Silveira, M. and Chapman, H. 2007. Cellular Expression Requirements for Inhibition of Type 1 Diabetes by a Dominantly Protective Major Histocompatibility Complex Haplotype.
Chen, Z. and Benoist, C. 2005. How defects in central tolerance impinge on a deficiency in regulatory T cells. Harvard Medical School.
Goudy, K. and Song, S. 2001. Adeno-associated virus vector-mediated IL-10 gene delivery prevents type 1 diabetes in NOD mice. Web.
Martinez, C. and Smith, J. 1963. Production of immunological Tolerance in Mice. University of Minnesota.
Murphy, K., Travers, P. and Janeway, C. 2008. Janeway’s immunobiology. Garland Science.
Jaeckel, E. and Klein, L. 2003. Normal Incidence of Diabetes in NOD Mice Tolerant to Glutamic Acid Decarboxylase. Harvard Medical School.