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Nicotine response genetics in the zebrafish

机译:斑马鱼的尼古丁反应遗传学

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摘要

Tobacco use is predicted to result in over 1 billion deaths worldwide by the end of the 21st century. How genetic variation contributes to the observed differential predisposition in the human population to drug dependence is unknown. The zebrafish (Danio rerio) is an emerging vertebrate model system for understanding the genetics of behavior. We developed a nicotine behavioral assay in zebrafish and applied it in a forward genetic screen using gene-breaking transposon mutagenesis. We used this method to molecularly characterize bdavl cct8 and hbog/gabbr1.2 as mutations with altered nicotine response. Each have a single human ortholog, identifying two points for potential scientific, diagnostic, and drug development for nicotine biology and cessation therapeutics. We show this insertional method generates mutant alleles that are reversible through Cre-mediated recombination, representing a conditional mutation system for the zebrafish. The combination of this reporter-tagged insertional muta-gen approach and zebrafish provides a powerful platform for a rich array of questions amenable to genetic-based scientific inquiry, including the basis of behavior, epigenetics, plasticity, stress, memory, and learning.
机译:据预测,到21世纪末,使用烟草会导致全球10亿多人死亡。遗传变异如何导致人们对药物依赖性的不同易感性尚不清楚。斑马鱼(Danio rerio)是一种新兴的脊椎动物模型系统,用于了解行为的遗传学。我们在斑马鱼中开发了一种尼古丁行为测定方法,并将其应用于使用破基因转座子诱变的正向遗传筛选中。我们使用这种方法将bdavl cct8和hbog / gabbr1.2分子表征为具有改变的尼古丁应答的突变。每个人都有一个人类直系同源物,为尼古丁生物学和戒断疗法的潜在科学,诊断和药物开发确定了两个要点。我们显示这种插入方法生成可通过Cre介导的重组可逆的突变等位基因,代表斑马鱼的条件突变系统。带有记者标记的插入式诱变方法和斑马鱼的结合为基于遗传的科学探究提供了一个强大的平台,可解决各种问题,包括行为,表观遗传学,可塑性,压力,记忆和学习的基础。

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