Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse
Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse
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DOI：
10.1073/pnas.231476798
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发表时间：
2001-11-06
影响因子：
11.1
通讯作者：
Alhenc-Gelas, F
中科院分区：
文献类型：
--
作者：
Huang, W;Gallois, Y;Alhenc-Gelas, F
糖尿病肾病是终末期肾脏疾病和心血管疾病的主要危险因素，具有显著的遗传成分。血管紧张素i转换酶（ACE）基因的一种常见变异（D等位基因）决定了较高的酶水平，与糖尿病肾病有关。为了解决这种关联背后的因果关系，我们在具有一个、两个或三个基因拷贝、血压正常、酶水平范围（野生型的65-162%）与人类相当的小鼠中诱导糖尿病。12周后，三拷贝糖尿病小鼠血压升高，并出现明显的蛋白尿。三拷贝糖尿病小鼠蛋白尿与血浆ACE水平相关。因此，ACE水平的适度遗传增加足以引起糖尿病小鼠的肾病。
Diabetic nephropathy is a major risk factor for end-stage renal disease and cardiovascular diseases and has a marked genetic component. A common variant (D allele) of the angiotensin I-converting enzyme (ACE) gene, determining higher enzyme levels, has been associated with diabetic nephropathy. To address causality underlying this association, we induced diabetes in mice having one, two, or three copies of the gene, normal blood pressure, and an enzyme level range (65-162% of wild type) comparable to that seen in humans. Twelve weeks later, the three-copy diabetic mice had increased blood pressures and overt proteinuria. Proteinuria was correlated to plasma ACE level in the three-copy diabetic mice. Thus, a modest genetic increase in ACE levels is sufficient to cause nephropathy in diabetic mice.