Quantitative trait loci affecting ethanol sensitivity in BXD recombinant inbred mice

Background: Genetic and environmental factors contribute to an individual's sensitivity to ethanol. although the exact genes underlying ethanol's effe cts are not known. Quantitative trait locus (QTL) mapping is one successful method for provisionally identifying genes participating in the mediation of a given behavior. QTL analyses seek to identify associations between a q uantitative response and previously mapped marker genes across genetically diverse individuals. Many QTL analyses have been performed in BXD recombina nt inbred (RI) strains of mice derived from a cross of C57BL/6J (B6) and DB A/2J (D2) progenitor strains. Methods: We conducted a QTL analysis of ethanol-induced loss of righting re flex and ataxia using a panel of 25 BXD RI strains and the progenitors B6 a nd D2. We measured the duration of loss of righting reflex after injection and blood ethanol concentrations upon regaining of righting reflex. Ataxia was measured as the latency to fall from a vertical screen. Results: Genome-wide QTL analyses correlating strain means with allelic sta tus at >1500 markers identified several associations (p less than or equal to 0.01). These provisional QTLs were on all chromosomes except 2, 5, 12, 1 3, and X, and several map near potential candidate genes. Conclusions: These results suggest that ethanol sensitivity is determined b y the actions of multiple genes and further suggest their general chromosom al map locations. These provisional linkages will now be confirmed or rejec ted using additional genetically segregating populations.