The quest for an animal model of diabetic nephropathy and the role of taurine deficiency.

Abstract

Diabetic nephropathy is the leading cause of end stage renal disease in man. Despite efforts, an ideal animal model that can reproduce the characteristics of human diabetic nephropathy has not been developed. To this end, we hypothesize that taurine deficiency is one of the critical risk factors for development of nephropathy in patients with diabetes mellitus. This hypothesis can be tested in vivo in TauT knockout (TauT −/−) C57BL/6 background mice. We asked whether taurine deficiency would enhance disease in the streptozotocin-treated mouse. We provide evidence that alteration of the TauT gene has a substantial effect on the susceptibility to diabetic kidney disease development in a TauT −/− mouse model of diabetes. These animals specifically developed characteristic renal histological changes that included glomerulosclerosis, nodular lesions, arteriosclerosis, arteriolar dilation, and tubulointerstitial fibrosis. Immunohistochemical staining of molecular markers such as smooth muscle actin, CD34, Ki67, and collagen IV confirmed these observations and were abnormal. The results demonstrated that TauT gene deletion predisposes C57BL/6 mice to develop end-stage diabetic kidney disease, which closely replicates the pathological features of diabetic nephropathy in human diabetic patients and, thus, can serve as a model for therapeutic strategies.