Matsumoto Akiko, Vasiliou Vasilis, Kawamoto Toshihiro, Tanaka Keitaro, Ichiba Masayoshi
Department of Social Medicine, Saga University, Saga, Japan.
Alcohol Clin Exp Res. 2014 Jul;38(7):1883-93. doi: 10.1111/acer.12462. Epub 2014 Jun 13.
The aldehyde dehydrogenase 2 (Aldh2) knockout mouse is an animal model of a polymorphism at the human ALDH2 locus (ALDH2*2). To detect differences in the basic phenotype of this animal model, lifespan, body weight (BW), and serum alanine aminotransferase (ALT) level were evaluated.
Aldh2(+/+) , Aldh2(+/-) , and Aldh2(-/-) mice were maintained, from 10 weeks of age, on standard solid food, with liquid supplied as ethanol (EtOH) solution at a concentration of 0 to 20% (forced EtOH consumption).
For animals provided with water (without EtOH), mice of the distinct genotypes exhibited no difference in lifespan, with the mean values ranging from 90 to 96 weeks for female mice and 97 to 105 weeks for male mice. For animals provided with EtOH, there was a dose-dependent reduction of lifespan in Aldh2(-/-) mice with p for trend <0.001. For example, the mean lifespans of the Aldh2(-/-) females in the 0, 3, 10, and 20% groups were 95, 85, 70, and 29 weeks, respectively. No influence on lifespan was found for Aldh2(+/+) and Aldh2(+/-) mice. BW and ALT level of Aldh2(-/-) mice were significantly lower than those of Aldh2(+/+) mice when the mice were treated with EtOH. While multiple regression analysis suggested that the BW and ALT level in Aldh2(-/-) mice correlated with lifespan, adjustment for EtOH concentration revealed that this correlation was not significant (i.e., reflected EtOH dependence).
Aldh2(-/-) mice were unchanged in terms of their basic phenotype under standard laboratory conditions. However, chronic EtOH administration (forced consumption) in these mice resulted in dose-dependent reductions in lifespan, BW, and serum ALT level.
醛脱氢酶2（Aldh2）基因敲除小鼠是人类ALDH2基因座（ALDH2*2）多态性的动物模型。为检测该动物模型基本表型的差异，对寿命、体重（BW）和血清丙氨酸氨基转移酶（ALT）水平进行了评估。
从10周龄开始，将Aldh2(+/+)、Aldh2(+/-)和Aldh2(-/-)小鼠饲养在标准固体食物上，并以浓度为0至20%的乙醇（EtOH）溶液作为液体供应（强制摄入乙醇）。
对于供应水（无乙醇）的动物，不同基因型的小鼠寿命无差异，雌性小鼠的平均值为90至96周，雄性小鼠为97至105周。对于供应乙醇的动物，Aldh2(-/-)小鼠的寿命呈剂量依赖性缩短，趋势p<0.001。例如，0%、3%、10%和20%组中Aldh2(-/-)雌性小鼠的平均寿命分别为95周、85周、70周和29周。未发现Aldh2(+/+)和Aldh2(+/-)小鼠的寿命受到影响。当用乙醇处理小鼠时，Aldh2(-/-)小鼠的体重和ALT水平显著低于Aldh2(+/+)小鼠。虽然多元回归分析表明Aldh2(-/-)小鼠的体重和ALT水平与寿命相关，但对乙醇浓度进行校正后发现这种相关性不显著（即反映了对乙醇的依赖性）。
在标准实验室条件下，Aldh2(-/-)小鼠的基本表型没有变化。然而，对这些小鼠进行慢性乙醇给药（强制摄入）会导致寿命、体重和血清ALT水平呈剂量依赖性降低。
