title: Knockout of the TauT gene predisposes C57BL/6 mice to streptozotocin-induced diabetic nephropathy.
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.
authors: 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.
authors: Xiaobin
authors: X
authors: Han
authors: 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.
authors: Andrea B
authors: AB
authors: Patters
authors: Department of Pharmacy, College of Pharmacy, Hyogo University, Kobe, Japan.
authors: Takashi
authors: T
authors: Ito
authors: Department of Pharmacy, College of Pharmacy, Hyogo University, Kobe, Japan.
authors: Junichi
authors: J
authors: Azuma
authors: Department of Pharmacology, University of South Alabama, Mobile, AL, United States of America.
authors: Stephen W
authors: SW
authors: Schaffer
authors: 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.
authors: Russell W
authors: RW
authors: Chesney
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D024141:Collagen Type IV / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000099247:Taurine Transporters
chemical_list: D000199:Actins; D024141:Collagen Type IV; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D000099247:Taurine Transporters
references: Diabetes Care. 2014;37(1):5-7
references: 24356590
references: Am J Clin Nutr. 1995 May;61(5):1115-9
references: 7733037
references: J Am Soc Nephrol. 2014 Jul;25(7):1415-29
references: 24676639
references: J Am Soc Nephrol. 2009 Dec;20(12):2503-12
references: 19729434
references: Cardiology. 1997 Mar-Apr;88(2):152-5
references: 9096915
references: Am J Physiol. 1999 Oct;277(4 Pt 1):E760-71
references: 10516137
references: Amino Acids. 2000;19(3-4):499-507
references: 11140355
references: Diabetes Care. 2007 Oct;30(10):2652-4
references: 17666467
references: Diabetes. 2005 Sep;54(9):2628-37
references: 16123351
references: J Nutr Metab. 2012;2012:476380
references: 22523672
references: Curr Diabetes Rev. 2007 May;3(2):103-10
references: 18220661
references: J Am Soc Nephrol. 2007 Feb;18(2):539-50
references: 17202420
references: N Engl J Med. 1993 Sep 30;329(14):977-86
references: 8366922
references: J Am Soc Nephrol. 2006 Jun;17(6):1501-2
references: 16672317
references: J Mol Cell Cardiol. 2008 May;44(5):927-37
references: 18407290
references: Kidney Int. 2010 May;77(9):749-50
references: 20393486
references: Am J Physiol Endocrinol Metab. 2009 Sep;297(3):E620-8
references: 19602579
references: Amino Acids. 2012 May;42(5):1529-39
references: 21437784
references: FASEB J. 2002 Feb;16(2):231-3
references: 11772953
references: Am J Physiol Renal Physiol. 2010 Mar;298(3):F788-95
references: 20042456
references: J Am Soc Nephrol. 2010 Sep;21(9):1533-42
references: 20634301
references: Pflugers Arch. 2006 Feb;451(5):668-77
references: 16249932
references: Diabetes. 2001 Oct;50(10):2363-75
references: 11574421
references: Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10190-5
references: 20479236
references: J Biol Chem. 2002 Oct 18;277(42):39266-73
references: 12163498
references: J Am Soc Nephrol. 2009 Jun;20(6):1323-32
references: 19423693
references: N Engl J Med. 2007 Jan 18;356(3):213-5
references: 17229948
references: PLoS One. 2010;5(3):e9923
references: 20360867
references: Eur J Pharmacol. 2008 Nov 12;597(1-3):75-80
references: 18796303