Diabetic nephropathy (DN) is one of the microvascular complications of both type 1 and type 2 diabetes, which is also associated with a poor life expectancy of diabetic patients. However, the pathogenesis of DN is still unclear. Thus, it is of great use to establish appropriate animal models of DN for doing research on pathogenesis and developing novel therapeutic strategies. Although a large number of murine models of DN including artificially induced, spontaneous, and genetically engineered (knockout and transgenic) animal models have been developed, none of them develops renal changes sufficiently reflecting those seen in humans. Here we review the identified murine models of DN from the aspects of genetic background, type of diabetes, method of induction, gene deficiency, animal age and gender, kidney histopathology, and phenotypic alterations in the hope of enhancing our comprehension of genetic susceptibility and molecular mechanisms responsible for this disease and providing new clues as to how to choose appropriate animal models of DN. 1. Introduction DN, as one complication of diabetes, is one of the leading causes of end-stage renal disease (ESRD) worldwide. The value of animal models in the study of pathogenesis is beyond doubt. Although great progress has been made in the study of animal models, none of the models can reproduce all the structural and functional changes of human DN. Murine models have substantial advantages over other species in the studies on pathogenesis of DN, including lower cost, murine repositories that bear multiple mutations, plentiful inbred strains, and an available map of murine genomic sequence on the Internet. The Animal Models of Diabetic Complications Consortium (AMDCC) proposes the following three criteria for a desirable murine model of DN: (1) more than 50% decline in glomerular filtration rate (GFR) over the lifetime of the animal; (2) greater than 10-fold increase in albuminuria compared with controls for that strain at the same age and gender; (3) histopathology findings which include mesangial sclerosis (a 50% increase in mesangial volume), any degree of arteriolar hyalinosis, glomerular basement membrane (GBM) thickening (a >25% increase compared with baseline by electron microscopy morphometry), and tubulointerstitial fibrosis. In fact, there are no murine models that meet all of the three criteria. Here we review the identified murine models of DN including artificially induced, spontaneous, and genetically engineered (knockout and transgenic) animal models and compare their advantages and
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