Transgenic mice are viable, fertile, and normal in size, display accelerated spontaneous diabetes onset in males, and have coat color pigmentation. Northern blot analysis and immunohistochemistry confirm pancreatic islet specific expression of the Ins1-Cat transgene. There is a 50-fold increase in catalase activity in transgenic islets when compared to wild-type controls, which approximates catalase activity normally found in the liver. Insulin and DNA content, insulin staining and islet morphology in transgenic animals is essentially the same as in wild-type controls.
Transgenic islets have a similar reactive oxygen species (ROS) level as wild-type controls in normal media. However, after exposure to cytokines there is a significant increase of ROS fluorescence in control islets, but much smaller increase in transgenic islets. Transgenic mice are resistant to diabetes when treated with streptozotocin or alloxan. Transgenic beta cells generate less ROS fluorescence when treated with hydrogen peroxide, superoxide or peroxynitrite, but surprisingly cyclophosphamide accelerates diabetes onset in transgenic mice.
This model provides a tool for looking at the role of oxidative stress in diabetes.
