Knockout of the TauT gene predisposes C57BL/6 mice to streptozotocin-induced diabetic nephropathy.
Knockout of the TauT gene predisposes C57BL/6 mice to streptozotocin-induced diabetic nephropathy.
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DOI：
10.1371/journal.pone.0117718
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chesney RW
中科院分区：
文献类型：
--
作者：
Han X;Patters AB;Ito T;Azuma J;Schaffer SW;Chesney RW
糖尿病肾病是世界上引起终末期肾病的主要原因。尽管已经做出了巨大的努力，但科学家们还没有找到能够复制人类糖尿病肾病特征的理想动物模型。在这项研究中，我们假设牛磺酸缺乏是糖尿病肾病发生的关键危险因素。这一假说在C57BL/6背景小鼠的紧张型杂合子(taut+/-)和纯合型(taut-/-)基因敲除中进行了体内验证。我们已经证明，Taut基因(也称为SLC6A6)的改变对Taut+/-和Taut-/-小鼠糖尿病模型发生广泛糖尿病肾脏疾病的易感性有实质性的影响。这些动物发生了人类糖尿病肾病特有的组织学变化，包括肾小球硬化、结节病变、动脉硬化、小动脉扩张和肾小管间质纤维化。平滑肌肌动蛋白、CD34、Ki67和IV型胶原分子标记物的免疫组织化学染色进一步证实了上述结果。我们的结果表明，纯合子和杂合子taut基因缺失均易使C57BL/6小鼠发生终末期糖尿病肾病，这与人类糖尿病肾病的病理特征密切相关。
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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