Use of genetic mouse models in the study of diabetic nephropathy

Abstract

The study of experimental diabetic nephropathy in rodent models has led to many changes in the clinical management of human diabetic nephropathy. With the development of technology to generate knockout and transgenic animals, the mouse has become a favored species in medical research. There are several genetic mouse models of diabetes, with the majority being models of type 2 diabetes mellitus. These include the hypoinsulinemic nonobese diabetic mouse, the KKAy mouse, the New Zealand obese mouse, the hyperinsulinemic ob/ob mouse, and the different strains of obese hyperinsulinemic db/db mouse. Each of these models displays some renal changes, but by far the best model of renal disease and the one that is the most studied is the db/db mouse. The db/db mouse displays substantial glomerular pathology, including mesangial matrix expansion and modest albuminuria. It has been reported that the db/db mouse has a decline in creatinine clearance after 5 months of age, but more specific approaches are warranted to confirm these findings. A number of intervention studies show renoprotection in this model. Although mice have many advantages, such as being able to be crossbred with genetically manipulated animals, in many ways they are not very similar to humans, and in some respects the rat may be a better choice, particularly in relation to some features of end-organ injury.