Knockout of the TauT Gene Predisposes C57BL/6 Mice to Streptozotocin-Induced Diabetic Nephropathy |
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| Authors: | Xiaobin Han Andrea B. Patters Takashi Ito Junichi Azuma Stephen W. Schaffer Russell W. Chesney |
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| Affiliation: | 1. Department of Pediatrics, University of Tennessee Health Science Center, and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Memphis, TN, United States of America.; 2. Department of Pharmacy, College of Pharmacy, Hyogo University, Kobe, Japan.; 3. Department of Pharmacology, University of South Alabama, Mobile, AL, United States of America.; Children’s Hospital Boston/Harvard Medical School, UNITED STATES, |
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| Abstract: | Diabetic nephropathy is the leading cause of end stage renal disease in the world. Although tremendous efforts have been made, scientists have yet to identify an ideal animal model that can reproduce the characteristics of human diabetic nephropathy. In this study, we hypothesize that taurine insufficiency is a critical risk factor for development of diabetic nephropathy associated with diabetes mellitus. This hypothesis was tested in vivo in TauT heterozygous (TauT+/-) and homozygous (TauT-/-) knockout in C57BL/6 background mice. We have shown that alteration of the TauT gene (also known as SLC6A6) has a substantial effect on the susceptibility to development of extensive diabetic kidney disease in both TauT+/- and TauT-/-mouse models of diabetes. These animals developed histological changes characteristic of human diabetic nephropathy that included glomerulosclerosis, nodular lesions, arteriosclerosis, arteriolar dilation, and tubulointerstitial fibrosis. Immunohistochemical staining of molecular markers of smooth muscle actin, CD34, Ki67 and collagen IV further confirmed these observations. Our results demonstrated that both homozygous and heterozygous TauT gene deletion predispose C57BL/6 mice to develop end-stage diabetic kidney disease, which closely replicates the pathological features of diabetic nephropathy in human diabetic patients. |
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