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Further Characterization and High-Resolution Mapping of Quantitative Trait Loci for Ethanol-Induced Locomotor Activity

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Abstract

Differential sensitivity to the stimulant effects of ethanol on locomotor activity is determined in part by genetic differences. Among inbred strains of mice, moderate doses of ethanol (1-2 g/kg) stimulate locomotor activity in some strains, e.g., the DBA/2J (D2), but only mildly affect activity in other strains, e.g., C57BL/6J (B6) (Crabbe et al., 1982, 1983; Crabbe, 1986; Dudek and Phillips, 1990; Dudek et al., 1991; Dudek and Tritto, 1994). Quantitative trait loci (QTL) for the acute ethanol (1.5 g/kg) locomotor response has been identified in the BXD recombinant inbred (RI) series (N = 25 strains), a C57BL/6J × DBA/2J (B6D2) F2 intercross (N = 1800), and heterogeneous stock (HS) mice (N = 550). QTLs detected (p < .01) in the RI series were found on chromosomes 1, 2, and 6 and these QTLs were expressed in a time-dependent fashion. The QTLs on chromosomes 1 and 2 were confirmed in the F2 intercross at p < 10−7 or better. HS mice from G32 to G35 were used to fine-map the chromosome 2 QTL. Compared to the consensus map, the genetic map in the HS animals was expanded 10- to 15-fold. Over the region flanked by D2Mit94 to D2Mit304, three separate QTLs were detected in the HS animals. The data obtained confirm the usefulness of HS mice for the fine-mapping of QTLs to a resolution of 2 cM or less.

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Authors and Affiliations

  1. Department of Neurobiology and Psychiatry, SUNY at Stony Brook, Stony Brook, New York, 11790

    Kristin Demarest

  2. Department of Psychiatry, SUNY at Stony Brook, Stony Brook, New York, 11790

    Jay Koyner, James McCaughran Jr., Laura Cipp & Robert Hitzemann

  3. Research and Psychiatry Services, Veterans Administration Medical Center, Northport, New York

    Robert Hitzemann

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  1. Kristin Demarest
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  2. Jay Koyner
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  4. Laura Cipp
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Demarest, K., Koyner, J., McCaughran, J. et al. Further Characterization and High-Resolution Mapping of Quantitative Trait Loci for Ethanol-Induced Locomotor Activity. Behav Genet 31, 79–91 (2001). https://doi.org/10.1023/A:1010261909853

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