Transgenic Zebra Finches: New Tool for Studying Learning and Brain Repair.

描述（由申请人提供）：这里提出的工作旨在建立我们迄今为止所取得的成果，以建立一种有效的生产转基因斑胸草雀的程序。斑胸草雀是一种鸣禽，它们通过模仿成年雀来学习鸣叫。调节这种行为的大脑区域是高度模块化的，并且在解剖学上有很好的定义；它们统称为“歌系”。在这个系统中，编码歌曲的关键神经元群在成年后不断被替换。解剖学和行为之间的紧密关系，加上不断替换产生行为的细胞的罕见能力，使歌唱系统成为研究学习和神经元替代的基本生物学的一个非常有吸引力的模型。几个关键资源已经和正在生成，以促进该系统的研究在越来越多的还原水平：该物种的基因组已经测序，cDNA文库已经生成，测序和发表，BAC文库已经创建并提供。这些资源有可能有助于阐明介导鸣叫行为的分子机制和细胞特性。然而，为了充分利用这些资源，必须有可能在体内操纵基因表达，这在斑胸草雀身上还做不到。在过去的一年里，本实验室将其资源用于开发这样一种工具，我们采用的方法使我们能够克服关键障碍并取得重大进展。这里概述了这一进展，以及我们将采取的步骤，以产生一种有效的方案，使转基因鸣禽。

DESCRIPTION (provided by applicant): The work proposed here is designed to build on what we have accomplished thus far toward establishing an efficient procedure for producing transgenic zebra finches. Zebra finches are songbirds that learn their song by imitating that of an adult. The brain regions that mediate this behavior are highly modular and well defined anatomically; they are collectively referred to as the "song system". Within this system a key population of neurons encoding the song is replaced continuously in adulthood. The tight relationship between anatomy and behavior, together with the rare ability to continuously replace those cells that produce the behavior, have made the song system a very attractive model for studying the basic biology of learning and neuronal replacement. Several key resources have been and are presently being generated to facilitate the study of this system at ever more reductionistic levels: the genome of this species has been sequenced, cDNA libraries have been generated, sequenced and published, and a BAC library has been created and made available. These resources have the potential to help elucidate the molecular mechanisms and cellular properties that mediate song behavior. However, to take full advantage of these resources it has to be possible to manipulate gene expression in vivo, which we cannot yet do in zebra finches. Over the last year this laboratory has devoted its resources to the development of such a tool, and the methods we have employed have allowed us to overcome key obstacles and make significant progress. That progress is outlined here as well as the steps we will take to produce an efficient protocol for making transgenic songbirds. PUBLIC HEALTH RELEVANCE: Neurogenesis and neuronal replacement occur in the context of song learning in adult zebra finches. This project is about the production of transgenic zebra finches that will help us understand the mechanisms, function and therapeutic potential of neuronal replacement in adult brain.