Rats are the smart choice: Rationale for a renewed focus on rats in behavioral genetics.

Rats are the smart choice: Rationale for a renewed focus on rats in behavioral genetics.
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DOI:
10.1016/j.neuropharm.2013.05.047
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发表时间:
2014-01
期刊:
影响因子:
4.7
通讯作者:
Palmer AA
Palmer AA
中科院分区:
医学2区
文献类型:
--
作者:
Parker CC;Chen H;Flagel SB;Geurts AM;Richards JB;Robinson TE;Solberg Woods LC;Palmer AA

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部分由于其丰富的行为库,大鼠已被广泛用于药物滥用相关性状的行为研究几十年。然而,在第一项小鼠研究发表后,小鼠成为研究人员探索成瘾遗传基础的首选模型,证明了通过胚胎干细胞技术改造小鼠基因组的能力。小鼠基因组的测序和最近对许多近交系小鼠品系的重新测序进一步巩固了小鼠作为遗传研究的首要哺乳动物生物体的地位。因此,许多最初为大鼠开发和优化的行为模式已经适应了小鼠。然而,许多复杂和有趣的药物滥用相关的行为,可以在大鼠中研究是非常困难的,或不可能适应用于小鼠,阻碍了这些特征的遗传解剖。现在,技术的进步已经消除了老鼠基因研究的许多历史局限性。例如,大鼠基因组已经测序,许多近交系大鼠品系现在正在重新测序,远交系大鼠种群正在用于精细定位QTL。此外,现在有可能使用锌指核酸酶(ZFN)、转录激活因子样效应物核酸酶(TALEN)和相关技术创建“敲除”大鼠。因此,大鼠现在可以用来进行复杂行为的定量遗传研究,这些行为在小鼠中很难或不可能进行研究。
Due in part to their rich behavioral repertoire rats have been widely used in behavioral studies of drug abuse-related traits for decades. However, the mouse became the model of choice for researchers exploring the genetic underpinnings of addiction after the first mouse study was published demonstrating the capability of engineering the mouse genome through embryonic stem cell technology. The sequencing of the mouse genome and more recent re-sequencing of numerous inbred mouse strains has further cemented the status of mice as the premier mammalian organism for genetic studies. As a result, many of the behavioral paradigms initially developed and optimized for rats have been adapted to mice. However, numerous complex and interesting drug abuse-related behaviors that can be studied in rats are very difficult or impossible to adapt for use in mice, impeding the genetic dissection of those traits. Now, technological advances have removed many of the historical limitations of genetic studies in rats. For instance, the rat genome has been sequenced and many inbred rat strains are now being re-sequenced and outbred rat stocks are being used to fine-map QTLs. In addition, it is now possible to create “knockout” rats using zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and related techniques. Thus, rats can now be used to perform quantitative genetic studies of sophisticated behaviors that have been difficult or impossible to study in mice.
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