title: Ethanol reduces lifespan, body weight, and serum alanine aminotransferase level of aldehyde dehydrogenase 2 knockout mouse.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Social Medicine, Saga University, Saga, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Vasilis
authors.initials: V
authors.lastname: Vasiliou
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Keitaro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ichiba
mesh_terms: D000410:Alanine Transaminase / Q000097:blood*; D000444:Aldehyde Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D001835:Body Weight / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005838:Genotype; D053208:Kaplan-Meier Estimate; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013997:Time Factors
chemical_list: D000431:Ethanol; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000410:Alanine Transaminase
keywords: Alanine Aminotransferase; Aldehyde Dehydrogenase 2; Ethanol; Lifespan; Polymorphism