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The Journal of Neuroscience, January 15, 1999, 19(2):549-561

Identification of an Acute Ethanol Response Quantitative Trait Locus on Mouse Chromosome 2

Kristin Demarest, James McCaughran Jr, Elham Mahjubi, Laura Cipp, and Robert Hitzemann

Departments of Psychiatry and Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York 11794-8101, and Research and Psychiatry Services, Veterans Administration Medical Center, Northport, New York 11768

A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) × DBA/2J (D2) F₂ intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F₂ analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (; ; ).

Key words: ethanol; mouse; genes; recombinant inbred; QTL; activity

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Copyright © 1999 Society for Neuroscience  0270-6474/99/192549-13$05.00/0

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