A grandparent-influenced locus for alcohol preference on mouse chromosome 2

Abstract

Objective 

Loci on mouse chromosome 2 have previously been associated with ethanol consumption. Here, we used a limited access choice paradigm in which mice consume large quantities of ethanol (2–3 g/kg/2 h) with a high preference (>80%). In addition, mouse chromosome substitution strains were used to further evaluate the contribution of chromosome 2 to ethanol consumption.

Methods and results 

First, we compared the two parental inbred mouse strains, C57BL/6J and A/J, in the limited access choice paradigm for ethanol intake and ethanol preference, as well as for ethanol metabolism and taste sensitivity. Then, the effect of chromosome 2 substitution on these measures was determined. Compared with C57BL/6J mice, A/J and C57BL/6J-Chr 2^A/NaJ (CSS-2) mice showed profoundly reduced ethanol intake and preference. The strains were not different with regard to ethanol metabolism or taste sensitivity. Limited access ethanol consumption in F₂ progeny derived from reciprocal C57BL/6J×CSS-2 and CSS-2×C57BL/6J intercrosses and subsequent quantitative trait loci mapping identified two loci: one locus on chromosome 2 for ethanol intake and a separate locus on distal chromosome 2 for ethanol preference. This latter locus was dependent on the grandparental origin.

Conclusion 

Using a limited access choice paradigm, we found that mouse chromosome 2 carries an allelic variant of a locus for ethanol intake and a distinct locus selective for ethanol preference. The heritability of alcoholism has been suggested to be parent-specific, perhaps resulting from genetic imprinting. Our findings suggest that grandparent-influenced vulnerability for ethanol consumption is conferred by genes on chromosome 2, providing important new leads to enhance our understanding of the heritability of alcoholism.