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/s11892-004-0053-1
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发表时间：
2004-12-01
影响因子：
4.2
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
在啮齿动物模型上进行实验性糖尿病肾病的研究，使人类糖尿病肾病的临床治疗发生了许多变化。随着产生基因敲除和转基因动物的技术的发展，小鼠已经成为医学研究中的热门物种。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。这些小鼠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，以及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了一些肾脏变化，但迄今为止最好的肾脏疾病模型和研究最多的是db/db小鼠。Db/db小鼠表现出实质性的肾小球病变，包括系膜基质扩张和适度的蛋白尿。据报道，db/db小鼠出生5个月后肌酐清除量下降，但需要更具体的方法来证实这些发现。许多干预研究表明，在这种模型中有肾脏保护作用。尽管小鼠有许多优势，比如能够与基因操纵的动物杂交，但它们在许多方面与人类不太相似，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 nonobese 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 crossbred 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.