Genetic and Pharmacologic Models for Type 1 Diabetes
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Abstract
Type 1 diabetes (T1D) is characterized by a partial or total insufficiency of insulin. The premiere animal model of autoimmune T cell?mediated T1D is the NOD mouse. A dominant negative mutation in the mouse insulin 2 gene ( Ins2 Akita ) produces a severe insulin deficiency syndrome without autoimmune involvement, as do a variety of transgenes overexpressed in beta cells. Pharmacologically induced T1D (without autoimmunity) elicited by alloxan or streptozotocin at high doses can generate hyperglycemia in almost any strain of mouse by direct toxicity. Multiple low doses of streptozotocin combine direct beta cell toxicity with local inflammation to elicit T1D in a male?sex?specific fashion. A summary of protocols relevant to the management of these different mouse models will be covered in this overview. Curr. Protoc. Mouse Biol. 3:9?19 © 2013 by John Wiley & Sons, Inc.
Keywords: mice; NOD; diabetes; alloxan; streptozotocin; beta cells
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PDF or HTML at Wiley Online LibraryTable of Contents
- Introduction
- The NOD Mouse
- The Akita Mouse: A Model of Insulin‐Responsive Diabetes without Insulitis
- Experimentally Induced Diabetes: Toxins
- Experimentally Induced Diabetes: Knockouts and Transgenes
- Experimentally Induced Diabetes: Viral Infection Models
- Notes and Conclusions
- Acknowledgments
- Literature Cited
- Figures
- Tables
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Figure 1. Histologic appearance of pancreatic islets in 5‐ to 6‐week‐old C57BL/6 wild‐type control (+/+) and heterozygous Ins2 Akita mice of both sexes. Insulin‐containing beta cells are stained with aldehyde fuchsin (blue color). Note the beta cell degranulation (loss of staining) in mutant mice of both sexes. At the time of necropsy, both mutant mice were hyperglycemic. At later ages, islets from severely hyperglycemic males are almost completely degranulated and markedly reduced in number; mutant females show a similar reduction in islet number, but more residual insulin‐positive beta cells per islet. View Image
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Literature Cited
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