NOD Mice—Good Model for T1D but Not Without Limitations

Abstract

The nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D) was discovered by coincidence in the 1980s and has since been widely used in the investigation of T1D and diabetic complications. The current in vivo study was originally designed to prospectively assess whether hyperglycemia onset is associated with physical destruction or functional impairment of beta cells under inflammatory insult during T1D progression in diabetes-prone female NOD mice. Prediabetic 16- to 20-wk-old NOD mice were transplanted with green fluorescent protein (GFP)-expressing reporter islets in the anterior chamber of the eye (ACE) that were monitored longitudinally, in addition to glycemia, with and without immune modulation using anti-CD3 monoclonal antibody therapy. However, there was an early and vigorous immune reaction against the GFP-expressing beta cells that lead to their premature destruction independent of autoimmune T1D development in progressor mice that eventually became hyperglycemic. This immune reaction also occurred in nonprogressor NOD recipients. These findings showed a previously unknown reaction of NOD mice to GFP that prevented achieving the original goals of this study but highlighted a new feature of the NOD mice that should be considered when designing experiments using this model in T1D research.

Reversal of diabetes by an oral Salmonella-based vaccine in acute and progressive diabetes in NOD mice

“…By 30 weeks of age, 77% of the mice were diabetic. Overall, the incidence of diabetes in female NOD mice in our study was somewhat less than reported [ 27 – 30 ]. This may be due to presence of Salmonella or other environmental factors [ 29 , 32 ].…”

Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices

“…The most common T1DM model, the NOD mouse, is prone to spontaneously developing autoimmune diabetes, which mimics many features of human disease such as, islet infiltration by immune cells (insulitis) and the development of autoantibodies [ 61 , 68 , 69 ]. It has been subjected to numerous successful experimental interventions, a majority of which have later failed in human clinical trials [ 68 ].…”

“…The most common T1DM model, the NOD mouse, is prone to spontaneously developing autoimmune diabetes, which mimics many features of human disease such as, islet infiltration by immune cells (insulitis) and the development of autoantibodies [ 61 , 68 , 69 ]. It has been subjected to numerous successful experimental interventions, a majority of which have later failed in human clinical trials [ 68 ]. Nonetheless, the number of similarities of human T1DM pathophysiology is astonishing, including similar polymorphisms that confer disease risk and the involvement of similar genes or biological pathways on the disease’s onset as well as immune response [ 68 , 70 ].…”

“…It has been subjected to numerous successful experimental interventions, a majority of which have later failed in human clinical trials [ 68 ]. Nonetheless, the number of similarities of human T1DM pathophysiology is astonishing, including similar polymorphisms that confer disease risk and the involvement of similar genes or biological pathways on the disease’s onset as well as immune response [ 68 , 70 ]. However, the translation of discoveries and therapies into humans has failed thus far.…”

Rodent Models to Analyze the Glioma Microenvironment

“…In NOD/ SCID mice, the SCID mutation (severe combined immunodeficiency) is combined with the NOD type (non-obese diabetic). SCID mutation homozygous animals do not form any T-or B-cells (with preserved myelopoiesis), and myeloid cells and natural killer (NK) cells functions can also be restricted In NOD mice, diabetes is caused by autoimmune reactions that cause the destruction of insulin-producing beta cells (Aldrich et al, 2020). Furthermore, polymorphisms of the Idd3 locus exist, that lead to increased IL-2 (IL ¼ interleukin) and IL-21 levels, which can influence the function of dendritic cells, B-cells, T-cells, and NK-cells (Wendt et al, 2007), and a mutation of the CTLA-4 gene (cytotoxic T-lymphocyteassociated Protein 4) results in an attenuated T-cell immune response (Ueda et al, 2003).…”