Advanced Diabetic Nephropathy Mouse Model
A major roadblock in development of new therapies for diabetic kidney disease is the absence of robust research models. In this project we investigated whether the combination of three key features of human disease (obesity, diabetes and high blood pressure) can be used to develop a better animal model.
A severe complication of diabetes, occurring in 20% to 40%, of diabetics is diabetic kidney disease (diabetic nephropathy or DN). DN is the major cause of chronic kidney disease where kidney transplant or dialysis becomes necessary. Since both outcomes have a huge negative impact on quality of life and are costly, the development of new medicines is urgently needed. However, this has been very difficult so far. One reason is the absence of good experimental disease models. The currently available models only mimic the early stages of the disease, whereas diagnosis in patients often occurs at a late stage of the disease. Therefore, there is an pressing need for development of a more translational model reflecting these more advanced disease stages.
In pilot experiments we showed that combining three key features (obesity, diabetes and hypertension) of the human disease resulted in the development of more advanced diabetic kidney disease in mice than seen in current models. In this project we have, together with pharmaceutical and technological partners, further characterized this new model. We investigated the contribution of the three key features to the development and progression of the disease and determined how the disease develops over time.
We compared disease development in males and females, compared different diets, dissected the role of hypertension, optimized experimental conditions, studied disease development of time, and showed that the model can be modulated with the current accepted clinical therapies.
We have proven that by combining obesity, diabetes and hypertension, an advanced stage of DN can be reached which shows all the typical clinical features and therefore is relevant new research model.
