A model for diabetic nephropathy: Advantages of the inducible cAMP early repressor transgenic mouse over the streptozotocin-induced diabetic mouse

We have previously found progressive diabetic nephropathy in inducible cAMP early repressor (ICER 1 gamma) transgenic (Tg) mice. The ICER 1 gamma Tg mouse is an interesting model of sustained hyperglycemia due to its low production of insulin and insulin-producing beta cells. Here in a longitudinal study we further analyzed diabetic nephropathy and structural and functional alterations in other organs, comparing our model with streptozotocin (STZ)-diabetic model mice. The high-dose STZ-diabetic model showed marked variation in blood glucose levels and severe toxicity of STZ in the liver and kidney. The low-dose STZ-diabetic model showed less toxicity, but the survival rate was very low. STZ-diabetic mice had much more variation of glomerular hypertrophy and sclerosis. Furthermore, non-specific toxicity of STZ or insulin injections to maintain optimal blood glucose levels might have another effect upon the diabetic renal changes. In contrast, ICER 1 gamma Tg mice exhibited a stable and progressive phenotype of diabetic kidney disease solely due to chronic hyperglycemia without other modulating factors. Thus, ICER 1 gamma Tg mouse has advantages for examining diabetic renal disease, and offers unique and very different perspectives compared to STZ model.