Alcohol preference in AXB/BXA recombinant inbred mice: gender differences and gender-specific quantitative trait loci

The purpose of the present study was to characterize the C57BL/6J, A/J, and AXB/BXA Recombinant Inbred (RI) strains of mice for voluntary alcohol cons umption. Quantitative Trait Locus (QTL) analysis was used to provide provis ional location of QTLs for alcohol consumption. The inbred strains were scr eened for levels of alcohol intake (calculated as alcohol preference and ab solute alcohol consumption) by receiving 4 days of forced exposure to a 10% (wt/vol) solution of alcohol, followed by 3 weeks of free choice between w ater and 10% alcohol. A wide and continuous distribution of values for alco hol consumption and preference was obtained in the AXB/BXA RI strains, conf irming polygenic influences on alcohol-related behaviors. Significant gende r differences were found for both alcohol preference F-28,F-651 = 2.12, p < 0.001] and absolute alcohol consumption [F-28,F-647 = 2.57, p < 0.001]. In males, putative QTLs were mapped to chromosomes (Chrs) 2, 5, 7, 10, 11, an d 16. Multiple regression analysis indicated that approximately 75% of the genetic variance in alcohol preference in males could be accounted for by t hree of the QTL regions. Several of the putative QTLs appeared to be male-s pecific (Tyr on Chr 7; D10Mit126 on Chr 10; D11Mit61 on Chr Il). In females , seven putative QTLs were mapped to Chrs 2, 4, 5, 7, 11, 16, and 19. Appro ximately 90% of the genetic variance in alcohol preference in females could be accounted for by four QTL regions, as determined by multiple regression . The QTL on Chr 11 near D11Mit35 appeared to be female-specific. This site was close to a female-specific QTL (Alcp2) previously mapped in C57BL/6J x DBA/2J backcrosses by Melo and coworkers (Nat Genet 13, 147, 1996). The QT Ls mapped for alcohol preference in the pre sent study must be considered s uggestive at the present time, since only D2Mit74 met very strict statistic al criteria for significance. However, the concordance across several studi es for the loci on Chrs 2, 4, 7, 9, and 11 suggest that some common QTLs in fluencing alcohol preference have been identified. Confirmation of QTLs map ped in the present study is currently being conducted in a new series of re combinant congenic (RC) strains developed from reciprocal backcrosses betwe en the A/J and C57BL/6J progenitors. The concomitant use of both RI and RC strains developed from the same progenitors should provide a powerful means of detecting, confirming, and mapping QTLs for alcohol-related traits.