Knockout of the TauT gene predisposes C57BL/6 mice to streptozotocin-induced diabetic nephropathy

Xiaobin Han, Andrea B. Patters, Takashi Ito, Junichi Azuma, Stephen W. Schaffer, Russell W. Chesney

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0117718
JournalPLoS One
Volume10
Issue number1
DOIs
StatePublished - Jan 28 2015
Externally publishedYes

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diabetic nephropathy
Gene Knockout Techniques
streptozotocin
Diabetic Nephropathies
gene targeting
Streptozocin
Inbred C57BL Mouse
Genes
Medical problems
kidney diseases
mice
Animals
Taurine
animal models
Muscle
Actins
Collagen
gene deletion
Chronic Kidney Failure
taurine

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Knockout of the TauT gene predisposes C57BL/6 mice to streptozotocin-induced diabetic nephropathy. / Han, Xiaobin; Patters, Andrea B.; Ito, Takashi; Azuma, Junichi; Schaffer, Stephen W.; Chesney, Russell W.

In: PLoS One, Vol. 10, No. 1, e0117718, 28.01.2015.

Research output: Contribution to journalArticle

Han, Xiaobin ; Patters, Andrea B. ; Ito, Takashi ; Azuma, Junichi ; Schaffer, Stephen W. ; Chesney, Russell W. / Knockout of the TauT gene predisposes C57BL/6 mice to streptozotocin-induced diabetic nephropathy. In: PLoS One. 2015 ; Vol. 10, No. 1.
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