An assay for evoked locomotor behavior in Drosophila reveals a role for integrins in ethanol sensitivity and rapid ethanol tolerance.
An assay for evoked locomotor behavior in Drosophila reveals a role for integrins in ethanol sensitivity and rapid ethanol tolerance.
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DOI：
10.1111/j.1530-0277.2009.01018.x
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Grotewiel M
中科院分区：
文献类型：
--
作者：
Bhandari P;Kendler KS;Bettinger JC;Davies AG;Grotewiel M
乙醇在哺乳动物和果蝇（Drosophila melanogaster）中诱导类似的行为反应。通过将乙醇相关行为的测定与果蝇中可用的遗传工具相结合，已经确定了一些影响乙醇生理反应的基因。为了提高果蝇模型在研究与乙醇相关行为相关的基因方面的实用性，我们探索了一种测定乙醇对负趋地性（一种诱发的运动反应）的镇静作用的测定方法的价值。我们建立了eRING（乙醇快速迭代负趋地性）作为一种测定方法，用于定量乙醇对负趋地性（即惊吓诱导的攀爬）的镇静作用。我们通过评估几种不同的对照菌株和具有已知破坏这些行为的突变的果蝇对乙醇的急性敏感性和快速乙醇耐受性来验证该测定。我们还在候选筛选中使用eRING来鉴定具有改变的乙醇相关行为的突变体。在eRING测定中测得的负趋地性受到乙醇暴露的剂量依赖性损害。在第二次暴露期间进行测试时，苍蝇对乙醇的致醉作用产生了耐受性。乙醇敏感性和快速乙醇耐受性在四个对照菌株中各不相同，但在第一次和第二次乙醇挑战期间，四种菌株的内部乙醇浓度无法区分。酒精敏感性和快速酒精耐受性分别在健忘和宿醉基因突变的果蝇中发生改变，这些基因已知会影响这些特征。此外，β整合素基因肌球蛋白和α整合素基因scab的突变增加了对乙醇的初始敏感性，并增强了快速乙醇耐受性的发展，而不改变内部乙醇浓度。eRING检测适用于研究影响乙醇敏感性和快速乙醇耐受性的遗传机制。果蝇的乙醇敏感性和快速乙醇耐受性依赖于α和β整合素的功能。
Ethanol induces similar behavioral responses in mammals and the fruit fly, Drosophila melanogaster. By coupling assays for ethanol-related behavior to the genetic tools available in flies, a number of genes have been identified that influence physiological responses to ethanol. To enhance the utility of the Drosophila model for investigating genes involved in ethanol-related behavior, we explored the value of an assay that measures the sedative effects of ethanol on negative geotaxis, an evoked locomotor response. We established eRING (ethanol Rapid Iterative Negative Geotaxis) as an assay for quantitating the sedative effects of ethanol on negative geotaxis (i.e. startle-induced climbing). We validated the assay by assessing acute sensitivity to ethanol and rapid ethanol tolerance in several different control strains and in flies with mutations known to disrupt these behaviors. We also used eRING in a candidate screen to identify mutants with altered ethanol-related behaviors. Negative geotaxis measured in eRING assays was dose-dependently impaired by ethanol exposure. Flies developed tolerance to the intoxicating effects of ethanol when tested during a second exposure. Ethanol sensitivity and rapid ethanol tolerance varied across four control strains, but internal ethanol concentrations were indistinguishable in the four strains during a first and second challenge with ethanol. Ethanol sensitivity and rapid ethanol tolerance, respectively, were altered in flies with mutations in amnesiac and hangover, genes known to influence these traits. Additionally, mutations in the β integrin gene myospheroid and the α integrin gene scab increased the initial sensitivity to ethanol and enhanced the development of rapid ethanol tolerance without altering internal ethanol concentrations. The eRING assay is suitable for investigating genetic mechanisms that influence ethanol sensitivity and rapid ethanol tolerance. Ethanol sensitivity and rapid ethanol tolerance depend on the function of α and β integrins in flies.
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影响因子：
2.9
作者：
Eckhardt, Christopher I.;Crane, Cory
通讯作者：
Crane, Cory
DOI：
10.1073/pnas.0712255105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Mani, Ramamurthy;Onge, Robert P. St.;Roth, Frederick P.
通讯作者：
Roth, Frederick P.
影响因子：
5.3
作者：
Chan, CS;Weeber, EJ;Davis, RL
通讯作者：
Davis, RL
影响因子：
3.3
作者：
LaFerriere, Holly;Guarnieri, Douglas J.;Zars, Troy
通讯作者：
Zars, Troy
影响因子：
64.8
作者：
Grotewiel, MS;Beck, CDO;Davis, RL
通讯作者：
Davis, RL