Voluntary alcohol consumption in BXD recombinant inbred mice: Relationship to alcohol metabolism

Voluntary alcohol consumption in BXD recombinant inbred mice: Relationship to alcohol metabolism
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DOI:
10.1111/j.1530-0277.1996.tb01063.x
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发表时间:
1996-02-01
影响因子:
3.2
通讯作者:
Deitrich, RA
Deitrich, RA
中科院分区:
医学3区
文献类型:
--
作者:
Gill, K;Liu, Y;Deitrich, RA

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开始研究C57 BL/6 J和DBA/2 J近交系小鼠以及衍生自它们的BXD重组近交系(RI)品系的行为和生化特征。C57 BL/6 J、DBA/2 J和7 BXD RI品系通过接受4天的10%(w/v)酒精溶液的强制暴露,随后在水和10%酒精之间自由选择3周来测试自愿酒精消耗(VAC)。VAC的测量包括酒精的绝对摄入量(g/kg)以及酒精偏好。各种BXD RI菌株显示了广泛的VAC,具有连续(而不是双峰)分布,表明参与调节酒精相关行为的几个基因可能具有累加效应。测定了C57 BL/6 J、DBA/2 J和BXD品系小鼠肝和脑中乙醛脱氢酶和过氧化氢酶的动力学特征,以验证酒精代谢酶水平的遗传调节介导VAC差异的假设。通过用Yellow Springs生物氧监测器和氧电极测量氧产生来测定过氧化氢酶活性。在BXD RI和亲本品系中,VAC和脑过氧化氢酶活性之间存在强烈的负相关。这些数据表明,RI株可能是有用的遗传模型,在检查控制VAC和其他响应酒精的数量性状基因座。
Studies were initiated to characterize behaviorally and biochemically C57BL/6J and DBA/2J inbred mice, as well as BXD Recombinant Inbred (RI) strains derived from them. The C57BL/6J, DBA/2J, and 7 BXD RI strains were tested for voluntary alcohol consumption (VAC) by receiving 4 days of forced exposure to a 10% (w/v) solution of alcohol, followed by 3 weeks of free choice between water and 10% alcohol, Measures of VAC included the absolute intake of alcohol (g/kg), as well as alcohol preference. A wide range of VAC was displayed by the various BXD RI strains with a continuous (rather than bimodal) distribution, indicating that there is likely to be additive effects of several genes involved in regulating alcohol-related behaviors. Kinetic characteristics of aldehyde dehydrogenase and catalase in liver and brain of the C57BL/6J, DBA/2J, and BXD strains of mice were determined to test the hypothesis that the genetic regulation of the levels of alcohol-metabolizing enzymes mediate differences in VAC, Aldehyde dehydrogenase activity was determined spectrophotometrically by observing the change in absorption at 340 nm. Catalase activity was determined by measuring oxygen production with a Yellow Springs Biological Oxygen monitor and oxygen electrode. There was a strong negative relationship between VAC and brain catalase activity in the BXD RI and parental strains. These data suggest that RI strains are likely to be useful genetic models in the examination of quantitative trait loci controlling VAC and other responses to alcohol.