Further characterization and high-resolution mapping of quantitative trait loci for ethanol-induced locomotor activity
Further characterization and high-resolution mapping of quantitative trait loci for ethanol-induced locomotor activity
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DOI：
10.1023/a:1010261909853
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发表时间：
2001-01-01
影响因子：
2.6
通讯作者：
Hitzemann, R
中科院分区：
文献类型：
--
作者：
Demarest, K;Koyner, J;Hitzemann, R
对乙醇对自发活动的刺激作用的不同敏感性部分由遗传差异决定。在近交系小鼠中，中等剂量的乙醇（1-2 g/kg）刺激某些品系小鼠的自发活动，例如，DBA/2 J（D2），但仅轻度影响其它菌株的活性，例如，C57 BL/6 J（B6）（Crabbe等人，1982，1983; Crabbe，1986; Dudek和菲利普斯，1990; Dudek等人，1991; Dudek和Tritto，1994）。急性乙醇（1.5 g/kg）运动反应的数量性状位点（QTL）已在BXD重组近交系（RI）系列（N = 25株）、C57 BL/6 J X DBA/2 J（B6 D2）F-2互交（N = 1800）和异质原种（HS）小鼠（N = 550）中鉴定。在RI系列中检测到的QTL（p <0.01）位于第1、2和6染色体上，并且这些QTL以时间依赖的方式表达。在F-2代互交中，在p < 10（-7）或更好的条件下，第1和第2染色体上的QTL被确定。从G（32）到G（35）的HS小鼠用于精细定位染色体2 QTL。与共有图谱相比，HS动物的遗传图谱扩展了10至15倍。在D2 Mit 94-D2 Mit 304侧翼区域，在HS动物中检测到三个独立的QTL。所获得的数据证实了HS小鼠用于QTL精细定位到2cM或更低分辨率的有用性。
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.