Crabbe J C, Belknap J K, Mitchell S R, Crawshaw L I
Research Service, VA Medical Center, Portland, Oregon.
J Pharmacol Exp Ther. 1994 Apr;269(1):184-92.
A recent method allows the identification of the rough genetic map location in mice of genes that exert modest effects on continuously distributed (i.e., quantitative) variables. Sensitivity and tolerance tolerance to the hypothermic effect of ethanol were studied with the purpose of identifying such quantitative trait loci (QTL). Mice from two progenitor inbred strains, C57BL/6J and DBA/2J, and 19 of their recombinant inbred (RI) BXD strains, were given ethanol daily for 3 days. By administering several doses of ethanol and recording multiple postdrug temperatures on the first and third injection day, the authors were able to compute several indices of initial sensitivity and tolerance magnitude in the RI strain battery. The strains differed at most times and doses in their acute reductions in body temperature with respect to their predrug base lines, which indicated genetic control of sensitivity to ethanol-induced hypothermia. The areas under the curve (which describes the initial hypothermic response over time), a measure that reflects both the maximal hypothermia achieved and the duration of total hypothermic response, also differed. The strains also differed in the magnitude of the tolerance developed to ethanol-induced hypothermia. Genetic determinants of sensitivity (and tolerance) to different doses of ethanol were primarily independent, although genetic sensitivity and tolerance to the intermediate (2- and 3-g/kg) doses were significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)
最近有一种方法可以确定小鼠中对连续分布（即定量）变量产生适度影响的基因的大致遗传图谱位置。为了确定此类数量性状基因座（QTL），研究了对乙醇低温效应的敏感性和耐受性。来自两个祖系近交系C57BL/6J和DBA/2J的小鼠以及它们的19个重组近交（RI）BXD品系，每天给予乙醇，持续3天。通过给予几种剂量的乙醇并记录第一次和第三次注射日的多个给药后体温，作者能够计算RI品系组中的几个初始敏感性和耐受程度指标。这些品系在大多数时间和剂量下，相对于给药前基线，其体温的急性降低情况有所不同，这表明对乙醇诱导的体温过低的敏感性存在遗传控制。曲线下面积（描述随时间的初始体温过低反应），这一反映达到的最大体温过低程度和总体温过低反应持续时间的指标，也有所不同。这些品系对乙醇诱导的体温过低产生的耐受程度也不同。对不同剂量乙醇的敏感性（和耐受性）的遗传决定因素主要是独立的，尽管对中间（2和3 g/kg）剂量的遗传敏感性和耐受性显著相关。（摘要截短于250字）
