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Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ x 129P3/J F2 intercross.

ABSTRACT: Consumption of ethanol solutions by rodents in two-bottle choice tests is a model to study human alcohol intake. Mice of the C57BL/6ByJ strain have higher ethanol preferences and intakes than do mice of the 129P3/J strain. F2 hybrids between these two strains were phenotyped using two-bottle tests involving a choice between water and either 3% or 10% ethanol. High ethanol preferences and intakes of the B6 mice were inherited as additive or dominant traits in the F2 generation. A genome screen using these F2 mice identified three significant linkages. Two loci, on distal chromosome 4 (Ap3q) and proximal chromosome 7 (Ap7q), strongly affected 10% ethanol intake and weakly affected 3% ethanol intake. A male-specific locus on proximal chromosome 8 (Ap8q) affected 3% ethanol preference, but not indexes of 10% ethanol consumption. In addition, six suggestive linkages (on chromosomes 2, 9, 12, 13, 17, and 18) affecting indexes of 3% and/or 10% ethanol consumption were detected. The loci with significant and suggestive linkages accounted for 35-44% of the genetic variation in ethanol consumption phenotypes. No additive-by-additive epistatic interactions were detected for the primary loci with significant and suggestive linkages. However, there were a few modifiers of the primary linkages and a number of interactions among unlinked loci. This demonstrates a significant role of the genetic background in the variation of ethanol consumption.

SUBMITTER: Bachmanov AA

PROVIDER: S-EPMC186641 | biostudies-literature | 2002 Aug

REPOSITORIES: biostudies-literature

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Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ x 129P3/J F2 intercross.

Bachmanov Alexander A AA Reed Danielle R DR Li Xia X Li Shanru S Beauchamp Gary K GK Tordoff Michael G MG

Genome research 20020801 8

Consumption of ethanol solutions by rodents in two-bottle choice tests is a model to study human alcohol intake. Mice of the C57BL/6ByJ strain have higher ethanol preferences and intakes than do mice of the 129P3/J strain. F2 hybrids between these two strains were phenotyped using two-bottle tests involving a choice between water and either 3% or 10% ethanol. High ethanol preferences and intakes of the B6 mice were inherited as additive or dominant traits in the F2 generation. A genome screen us ...[more]

PMID: 12176933

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Project description:BackgroundIn recent years, much attention has been given to the lack of reproducibility in biomedical research, particularly in preclinical animal studies. This is a problem that also plagues the alcohol research field, particularly in consistent consumption in animal models of alcohol use disorders. One often overlooked factor that could affect reproducibility is the maintenance diet used in preclinical studies.MethodsHerein, 2 well-established models of alcohol consumption, the "drinking in the dark" (DID) procedure and the continuous 2-bottle choice (C2BC) paradigm, were employed to determine the effects of diet on ethanol (EtOH) consumption. Male C57BL/6J mice were given 1 of 6 standard rodent chow diets obtained from Purina LabDiet(®) , Inc. (Prolab(®) RMH 3000) or Harlan(®) Laboratories, Inc. (Teklad Diets T.2916, T.2918, T.2920X, T.7912, or T.8940). A separate group of animals were used to test dietary effects on EtOH pharmacokinetics and behavioral measures following intraperitoneal (IP) injections of various doses of EtOH.ResultsMice eating Harlan diets T.2916 (H2916) and T.2920X (H2920) consumed significantly less EtOH and exhibited lower blood EtOH concentrations (BECs) during DID; however, during C2BC, animals maintained on Harlan T.7912 (H7912) consumed more EtOH and had a higher EtOH preference than the other diet groups. EtOH consumption levels did not stem from changes in alcohol pharmacokinetics, as a separate group of animals administered EtOH IP showed no difference in BECs. However, animals on Harlan diet T.2920X (H2920) were more sensitive to alcohol-induced locomotor activity in an open-field task. No diet-dependent differences were seen in alcohol-induced sedation as measured with loss of righting reflex.ConclusionsAlthough these data do not identify a specific mechanism, together, they clearly show that the maintenance diet impacts EtOH consumption. It is incumbent upon the research community to consider the importance of describing nutritional information in methods, which may help decrease interlaboratory reproducibility issues.

Dataset Information

Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ x 129P3/J F2 intercross.

Publications

Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ x 129P3/J F2 intercross.

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