Further characterization and high-resolution mapping of quantitative trait loci for ethanol-induced locomotor activity

被引:77
作者
Demarest, K
Koyner, J
McCaughran, J
Cipp, L
Hitzemann, R
机构
[1] SUNY Stony Brook, Dept Neurobiol & Psychiat, Stony Brook, NY 11790 USA
[2] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11790 USA
[3] Vet Adm Med Ctr, Res Serv, Northport, NY 11768 USA
[4] Vet Adm Med Ctr, Psychiat Serv, Northport, NY 11768 USA
关键词
QTL; mouse; ethanol; activity; recombinant inbred; fine-mapping;
D O I
10.1023/A:1010261909853
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
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 X DBA/2J (B6D2) F-2 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 F-2 intercross at p < 10(-7) or better. HS mice from G(32) to G(35) 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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页码:79 / 91
页数:13
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