Genetic and Pharmacologic Models for Type 1 Diabetes

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.