Ernest Gallo Clinic and Research Center, Department of Neurology, University of California San Francisco Emeryville, California 94608.
Brain Behav. 2012 Jan;2(1):22-31. doi: 10.1002/brb3.29.
Although genetic background alters responses to ethanol, there has not yet been a methodical quantification of differences in ethanol-related behaviors between inbred and hybrid mice commonly used in gene-targeting studies. Here, we compared C57BL/6NTac × 129S6/SvEvTac F1 hybrid mice (B6129S6) with C57BL/6NTac inbred mice (B6NT), and C57BL/6J × 129X1/SvJ (B6129X1) and C57BL/6J × 129S4/SvJae F1 hybrids (B6129S4) with C57BL/6J mice (B6J), in five commonly used tests: continuous access two-bottle choice drinking, intermittent limited-access binge drinking, ethanol clearance, ethanol-induced loss of the righting reflex, and conditioned place preference (CPP) for ethanol. We found that inbred B6J and B6NT mice showed greater ethanol preference and consumption than their respective hybrids when ethanol was continuously available. Within the intermittent limited-access drinking procedure, though all lines showed similar intake over eight drinking sessions, the average of all sessions showed that B6NT mice drank significantly more ethanol than B6129S6 mice. In addition, B6J mice consumed more ethanol than B6129X1 mice, although they drank less than B6129S4 mice. No differences in ethanol LORR duration were observed between inbred and hybrid mice. Although ethanol clearance was similar among B6J mice and their respective hybrids, B6NT mice cleared ethanol more rapidly than B6129S6 mice. All lines developed CPP for ethanol. Our findings indicate that it may not be necessary to backcross hybrids to an inbred B6 background to study many ethanol-related behaviors in gene-targeted mice.
虽然遗传背景会改变对乙醇的反应，但目前还没有系统地量化基因靶向研究中常用的近交系和杂交小鼠在乙醇相关行为上的差异。在这里，我们比较了 C57BL/6NTac × 129S6/SvEvTac F1 杂交小鼠（B6129S6）与 C57BL/6NTac 近交系小鼠（B6NT），以及 C57BL/6J × 129X1/SvJ（B6129X1）和 C57BL/6J × 129S4/SvJae F1 杂交小鼠（B6129S4）与 C57BL/6J 小鼠（B6J）在五个常用测试中的差异：连续双瓶选择饮酒、间歇性限时 binge 饮酒、乙醇清除率、乙醇诱导的翻正反射丧失和乙醇条件性位置偏好（CPP）。我们发现，当乙醇持续供应时，近交系 B6J 和 B6NT 小鼠比各自的杂交系表现出更高的乙醇偏好和消耗。在间歇性限时饮酒程序中，尽管所有品系在八次饮酒过程中表现出相似的摄入量，但在所有阶段的平均水平上，B6NT 小鼠的饮酒量明显高于 B6129S6 小鼠。此外，B6J 小鼠的饮酒量多于 B6129X1 小鼠，尽管它们的饮酒量少于 B6129S4 小鼠。近交系和杂交系小鼠之间的乙醇 LORR 持续时间没有差异。尽管 B6J 小鼠与其各自的杂交系之间的乙醇清除率相似，但 B6NT 小鼠的乙醇清除速度快于 B6129S6 小鼠。所有品系都对乙醇产生 CPP。我们的研究结果表明，在研究基因靶向小鼠的许多乙醇相关行为时，可能不必将杂交系回交至近交系 B6 背景。
