Howard Hughes Medical Institute, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University Atlanta, GA, USA.
Front Mol Neurosci. 2009 Nov 30;2:22. doi: 10.3389/neuro.02.022.2009. eCollection 2009.
The use of conventional knockout technologies has proved valuable for understanding the role of key genes and proteins in development, disease states, and complex behaviors. However, these strategies are limited in that they produce broad changes in gene function throughout the neuroaxis and do little to identify the effects of such changes on neural circuits thought to be involved in distinct functions. Because the molecular functions of genes often depend on the specific neuronal circuit in which they are expressed, restricting gene manipulation to specific brain regions and times may be more useful for understanding gene functions. Conditional gene manipulation strategies offer a powerful alternative. In this report we briefly describe two conditional gene strategies that are increasingly being used to investigate the role of genes in behavior - the Cre/loxP recombination system and lentiviral vectors. Next, we summarize a number of recent experiments which have used these techniques to investigate behavior after spatial and/or temporal and gene manipulation. These conditional gene targeting strategies provide useful tools to study the endogenous mechanisms underlying complex behaviors and to model disease states resulting from aberrant gene expression.
传统的基因敲除技术已被证明对理解关键基因和蛋白质在发育、疾病状态和复杂行为中的作用具有重要价值。然而，这些策略存在局限性，因为它们会在整个神经轴上产生广泛的基因功能变化，而且几乎无法确定这些变化对被认为参与特定功能的神经回路的影响。由于基因的分子功能通常取决于它们在其中表达的特定神经元回路，因此将基因操作限制在特定的脑区和时间可能更有助于理解基因功能。条件性基因操作策略提供了一种强大的替代方法。在本报告中，我们简要描述了两种越来越多地用于研究基因在行为中的作用的条件性基因操作策略——Cre/loxP 重组系统和慢病毒载体。接下来，我们总结了一些最近使用这些技术研究空间和/或时间和基因操作后行为的实验。这些条件性基因靶向策略为研究复杂行为的内在机制以及模拟异常基因表达引起的疾病状态提供了有用的工具。
