Crabbe J C
Portland Alcohol Research Center, Department of Veterans Affairs, Oregon, USA.
J Pharmacol Exp Ther. 1998 Jul;286(1):263-71.
Male mice from C57BL/6J (B6), DBA/2J (D2) and their 25 recombinant inbred (RI) strains were exposed to ethanol (EtOH) vapor (3.0-9.0 mg EtOH/liter of air) for 72 hr. Mice were selected such that each strain averaged 1.34 to 1.59 mg of EtOH/ml of blood on withdrawal. Control groups and EtOH-exposed groups were tested hourly for handling-induced convulsions (HIC) for 10 hr and at hr 24 and 25. Strain withdrawal severity was indexed as the area under the 25-hr HIC curve for the EtOH group minus that strain's equivalent value for the control group. Genome-wide quantitative trait locus (QTL) analyses correlating strain means with allelic status at > 1500 markers identified 10 chromosomal regions at P < .01. These provisionally identified QTLs were on chromosomes 1 (2 QTLs), 3, 9 (2 QTLs), 10, 12, 13, 15 and 18. Multiple regression analysis using the four most influential QTLs revealed that these loci controlled 86% of the genetic variance. A QTL mapped to distal chromosome 1 (P < .001) is in the same region as one previously definitively mapped for acute alcohol withdrawal, as well as one mapped for acute pentobarbital withdrawal. Several of the QTLs map near potential candidate genes. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.
将C57BL/6J（B6）、DBA/2J（D2）雄性小鼠及其25个重组近交（RI）品系暴露于乙醇（EtOH）蒸汽（3.0 - 9.0毫克EtOH/升空气）中72小时。选择小鼠，使每个品系在戒断时血液中EtOH平均含量为1.34至1.59毫克/毫升。对对照组和乙醇暴露组每小时进行一次处理诱导惊厥（HIC）测试，持续10小时，并在第24小时和第25小时进行测试。品系戒断严重程度以乙醇组25小时HIC曲线下面积减去该品系对照组的等效值来衡量。全基因组数量性状位点（QTL）分析将品系均值与超过1500个标记的等位基因状态相关联，确定了10个染色体区域，P < 0.01。这些初步确定的QTL位于染色体1（2个QTL）、3、9（2个QTL）、10、12、13、15和18上。使用四个最具影响力的QTL进行的多元回归分析表明，这些位点控制了86%的遗传变异。一个定位到染色体1远端的QTL（P < 0.001）与之前确定的急性酒精戒断定位区域相同，也与急性戊巴比妥戒断定位区域相同。几个QTL位于潜在候选基因附近。现在将使用额外的遗传分离群体来确认或否定这些初步的连锁关系。
