Characteristics of aldehyde dehydrogenase 2 (Aldh2) knockout mice
Characteristics of aldehyde dehydrogenase 2 (Aldh2) knockout mice
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DOI：
10.3109/15376510903401708
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发表时间：
2009-11
影响因子：
3.2
通讯作者：
Hsu-Sheng Yu;T. Oyama;T. Isse;Kyoko Kitakawa;M. Ogawa;T. Pham;T. Kawamoto
中科院分区：
文献类型：
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作者：
Hsu-Sheng Yu;T. Oyama;T. Isse;Kyoko Kitakawa;M. Ogawa;T. Pham;T. Kawamoto
乙醛是乙醇氧化的中间体。它与DNA共价结合，被称为致癌物质。乙醛脱氢酶2（ALDH 2）是一种重要的氧化乙醛的酶。大约45%的中国和日本个体具有失活ALDH 2基因型（ALDH 2 *2/*2和ALDH 2 *1/*2），并且Aldh 2敲除小鼠似乎是具有失活ALDH 2的人类的有效动物模型。本文综述了已发表的研究Aldh 2基因敲除小鼠，这是治疗与乙醇或乙醛。根据这些研究，发现Aldh 2 −/−小鼠（Aldh 2敲除小鼠）比Aldh 2 +/+小鼠（野生型小鼠）更容易受到乙醇和乙酰丙酮诱导的毒性。当用乙醇喂养小鼠时，死亡率增加。当它们暴露在含有乙醛的空气中时，与Aldh 2 +/+小鼠相比，Aldh 2 −/−小鼠表现出更严重的毒性症状，如体重减轻和血液乙醛水平升高。因此，乙醇和乙醛处理对Aldh 2敲除小鼠的影响大于野生型小鼠。基于这些发现，可以推断乙醇消耗和乙醛吸入对ALDH 2非活性人类构成更高的风险。这些结果也支持了习惯性饮酒的ALDH 2缺陷的人比具有功能性ALDH 2的人具有更高的癌症发病率。
Acetaldehyde is an intermediate of ethanol oxidation. It covalently binds to DNA, and is known as a carcinogen. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals have the inactive ALDH2 genotypes (ALDH2*2/*2 and ALDH2*1/*2), and Aldh2 knockout mice appear to be a valid animal model for humans with inactive ALDH2. This review gives an overview of published studies on Aldh2 knockout mice, which were treated with ethanol or acetaldehyde. According to these studies, it was found that Aldh2 −/− mice (Aldh2 knockout mice) are more susceptible to ethanol and acetaldehyde-induced toxicity than Aldh2 +/+ mice (wild type mice). When mice were fed with ethanol, the mortality was increased. When they were exposed to atmospheres containing acetaldehyde, the Aldh2 −/− mice showed more severe toxic symptoms, like weight loss and higher blood acetaldehyde levels, as compared with the Aldh2 +/+ mice. Thus, ethanol and acetaldehyde treatment affects Aldh2 knockout mice more than wild type mice. Based on these findings, it is suggested that ethanol consumption and acetaldehyde inhalation are inferred to pose a higher risk to ALDH2-inactive humans. These results also support that ALDH2-deficient humans who habitually consume alcohol have a higher rate of cancer than humans with functional ALDH2.