NOD Mice-Good Model for T1D but Not Without Limitations.

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.

Correction to: In vivo imaging of type 1 diabetes immunopathology using eye-transplanted islets in NOD mice.

Unfortunately there is a mistake in the presentation of the affiliations in this paper.

In vivo imaging of type 1 diabetes immunopathology using eye-transplanted islets in NOD mice.

AIMS/HYPOTHESIS: Autoimmune attack against the insulin-producing beta cells in the pancreatic islets results in type 1 diabetes. However, despite considerable research, details of the type 1 diabetes immunopathology in situ are not fully understood mainly because of difficult access to the pancreatic islets in vivo. METHODS: Here, we used direct non-invasive confocal imaging of islets transplanted in the anterior chamber of the eye (ACE) to investigate the anti-islet autoimmunity in NOD mice before, during and after diabetes onset. ACE-transplanted islets allowed longitudinal studies of the autoimmune attack against islets and revealed the infiltration kinetics and in situ motility dynamics of fluorescence-labelled autoreactive T cells during diabetes development. Ex vivo immunostaining was also used to compare immune cell infiltrations into islet grafts in the eye and kidney as well as in pancreatic islets of the same diabetic NOD mice. RESULTS: We found similar immune infiltration in native pancreatic and ACE-transplanted islets, which established the ACE-transplanted islets as reliable reporters of the autoimmune response. Longitudinal studies in ACE-transplanted islets identified in vivo hallmarks of islet inflammation that concurred with early immune infiltration of the islets and preceded their collapse and hyperglycaemia onset. A model incorporating data on ACE-transplanted islet degranulation and swelling allowed early prediction of the autoimmune attack in the pancreas and prompted treatments to intercept type 1 diabetes. CONCLUSIONS/INTERPRETATION: The current findings highlight the value of ACE-transplanted islets in studying early type 1 diabetes pathogenesis in vivo and underscore the need for timely intervention to halt disease progression.