Use of genetic mouse models in the study of diabetic nephropathy.
Use of genetic mouse models in the study of diabetic nephropathy.
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DOI：
10.1007/s11883-004-0032-7
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发表时间：
2004-05-01
影响因子：
5.8
通讯作者：
Lan, Hui Y
中科院分区：
文献类型：
--
作者：
Allen, Terri J;Cooper, Mark E;Lan, Hui Y
在啮齿动物模型中对实验性糖尿病肾病的研究导致了人类糖尿病肾病临床管理的许多变化。随着基因敲除和转基因动物技术的发展，小鼠已成为医学研究的热门物种。有几种糖尿病的遗传小鼠模型，其中大多数是2型糖尿病的模型。这些包括低胰岛素血症非肥胖糖尿病小鼠、Kkay小鼠、新西兰肥胖小鼠、高胰岛素血症ob/ob小鼠和不同品系的肥胖高胰岛素血症db/db小鼠。这些模型中的每一个都显示出一些肾脏变化，但迄今为止，最好的肾脏疾病模型和研究最多的模型是db/db小鼠。db/db小鼠表现出显著的肾小球病理学，包括系膜基质扩张和适度的白蛋白尿。据报道，db/db小鼠在5月龄后肌酐清除率下降，但需要更具体的方法来证实这些发现。一些干预研究表明，在这个模型中肾保护。虽然小鼠有许多优点，例如能够与基因操纵的动物杂交，但在许多方面它们与人类并不非常相似，在某些方面，大鼠可能是更好的选择，特别是在终末器官损伤的某些特征方面。
The study of experimental diabetic nephropathy in rodent models has led to many changes in the clinical management of human diabetic nephropathy. With the development of technology to generate knockout and transgenic animals, the mouse has become a favored species in medical research. There are several genetic mouse models of diabetes, with the majority being models of type 2 diabetes mellitus. These include the hypoinsulinemic non-obese diabetic mouse, the Kkay mouse, the New Zealand obese mouse, the hyperinsulinemic ob/ob mouse, and the different strains of obese hyperinsulinemic db/db mouse. Each of these models displays some renal changes, but by far the best model of renal disease and the one that is the most studied is the db/db mouse. The db/db mouse displays substantial glomerular pathology, including mesangial matrix expansion and modest albuminuria. It has been reported that the db/db mouse has a decline in creatinine clearance after 5 months of age, but more specific approaches are warranted to confirm these findings. A number of intervention studies show renoprotection in this model. Although mice have many advantages, such as being able to be cross-bred with genetically manipulated animals, in many ways they are not very similar to humans, and in some respects the rat may be a better choice, particularly in relation to some features of end-organ injury.