Nicotine response genetics in the zebrafish
Nicotine response genetics in the zebrafish
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DOI：
10.1073/pnas.0908247106
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发表时间：
2009-11-03
影响因子：
11.1
通讯作者：
Ekker, Stephen C.
中科院分区：
文献类型：
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作者：
Petzold, Andrew M.;Balciunas, Darius;Ekker, Stephen C.
据预测，到21（st）世纪末，烟草使用将导致全世界超过10亿人死亡。遗传变异如何促成在人群中观察到的药物依赖性的不同倾向尚不清楚。斑马鱼（Danio rerio）是一种新兴的脊椎动物模型系统，用于理解行为的遗传学。我们开发了一种斑马鱼尼古丁行为检测方法，并将其应用于基因断裂转座子诱变的正向遗传筛选。我们用这种方法从分子水平上表征了bdav/cct 8和hbog/gabbr 1.2作为尼古丁反应改变的突变。每一种都有一个人类直系同源物，为尼古丁生物学和戒烟疗法的潜在科学，诊断和药物开发确定了两个点。我们表明，这种插入方法产生的突变等位基因是可逆的，通过铬介导的重组，代表了斑马鱼的条件突变系统。这种标记的插入诱变剂方法和斑马鱼的结合为丰富的问题提供了一个强大的平台，这些问题适合于基于遗传学的科学探究，包括行为的基础，表观遗传学，可塑性，压力，记忆和学习。
Tobacco use is predicted to result in over 1 billion deaths worldwide by the end of the 21(st) 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 bdav/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 mutagen 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.