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 it will be investigate 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 can develop into kidney failure, 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 could be showed that the combination of 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 this new model will be further characterized. We will investigate the contribution of the three key features to the development and progression of the disease and determine how the disease develops over time.

It is anticipated that the advanced model of DN will give insight in the underlying processes involved in development and progression of diabetic nephropathy, can guide identification of new biomarkers for early diagnosis and progression of the disease, and can contribute to the development of new therapeutic interventions.