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Diminished alcohol preference in transgenic mice lacking aldehyde dehydrogenase activity
Toyohi Isse1, Tsunehiro Oyama, Kyoko Kitagawa
1Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu Japan.
Pharmacogenetics
|November 20, 2002
Summary
Mice lacking aldehyde dehydrogenase (ALDH) 2 showed alcohol avoidance. This suggests ALDH2 genotype directly impacts alcohol preference, with brain acetaldehyde levels correlating to avoidance.
Area of Science:
- Biochemistry
- Genetics
- Neuroscience
Background:
- Aldehyde dehydrogenase (ALDH) 2 is crucial for aldehyde detoxification and influences alcohol preference.
- Mutations in the Aldh2 gene lead to reduced enzyme activity, causing increased alcohol sensitivity and lower tolerance in humans.
- The genetic basis for alcohol preference versus avoidance in different mouse strains remains unclear.
Purpose of the Study:
- To investigate the role of the Aldh2 gene in determining alcohol preference.
- To explore the correlation between brain acetaldehyde concentration and alcohol avoidance.
- To establish an animal model for studying alcoholism and alcohol-related diseases.
Main Methods:
- Creation of Aldh2-negative (Aldh2-/-) mice by genetically knocking out the Aldh2 gene in a high alcohol preference C57BL/6 background.
- Free-choice drinking tests with ethanol and water.
- Measurement of acetaldehyde concentrations in the brain and liver.
Main Results:
- Aldh2-/- mice displayed a characteristic alcohol avoidance.
- Despite drinking less ethanol, Aldh2-/- mice had brain and liver acetaldehyde concentrations comparable to wild-type (Aldh2+/+) mice.
- A direct effect of Aldh2 genotype on alcohol preference was indicated.
Conclusions:
- The Aldh2 genotype plays a significant role in determining alcohol preference.
- Brain acetaldehyde concentration is correlated with alcohol avoidance.
- Aldh2-deficient mice serve as a valuable model for alcoholism research.