Transgenesis in songbirds for the genetic manipulation of neuronal circuits

用于神经元回路遗传操纵的鸣禽转基因

基本信息

批准号：
8031501
负责人：
CARLOS LOIS
金额：
$ 33.67万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8031501
关键词：
Achievement Adult Affect Animal Model Animals Automobile Driving Behavior Behavioral Biological Birds Blastoderm Boxing Brain Brain region Breeding Cell Culture Techniques Cell Nucleus Cells Communication impairment Complex Derivation procedure Development Disease Embryo Enhancers Exhibits Finches Gene Delivery Gene Expression Gene Targeting Gene Transfer Techniques Generations Genes Genome Germ Cells Green Fluorescent Proteins Health Hormonal Human In Vitro Infection Investigation Laboratories Learning Lentivirus Vector Mediating Mental disorders Methods Modeling Modification Molecular Neurobiology Neurons Partner in relationship Physiological Population Principal Investigator Production Prosencephalon Proteins Recombinants Regulator Genes Regulatory Element Sleep Songbirds Speech Structure of primordial sex cell Subfamily lentivirinae System Techniques Technology Testing Transfection Transgenes Transgenic Organisms Viral Vector adult neurogenesis base blastomere structure cell type cognitive function egg genetic manipulation human disease improved lentiviral-mediated mind control nervous system disorder novel promoter selective expression sex tool transgene expression transmission process vocal learning zebra finch

项目摘要

DESCRIPTION (provided by applicant): Songbirds have been a rich experimental system for studying neurobiological questions of relevance to human health for decades. In particular, songbirds are the leading non-human model for the investigation of the biological basis of vocal learning, a critical behavioral substrate for speech acquisition. In addition, songbirds are an ideal system for the study of brain asymmetry, hormonal control of brain development, physiological function of sleep, and sex-specific differences in the brain, behavioral-induced gene expression and adult neurogenesis, among other questions. Nonetheless despite their importance for neurobiology, the usefulness of songbirds as an experimental system has been restricted by a lack of genetic manipulation methods. Recently we have succeeded in applying lentiviral-mediated transgenesis to zebra finches (Agate et al., 2009). While this achievement proves the feasibility of lentiviral-mediated transgenesis in songbirds, the current method is inefficient, labor-intensive and costly. In this proposal we plan to optimize the existing strategy and to generate novel tools to develop a practical avian transgenic technique that could be used by other songbird neurobiology laboratories. The ability to perform genetic manipulations in songbirds will open unparalleled opportunities for the study of the relationship between genes and brain function in an animal species with a robust behavioral repertoire. Transgenic songbirds will allow us to generate animal models of human diseases affecting complex cognitive functions and communication disorders, which can only be incompletely modeled in other animal species. PUBLIC HEALTH RELEVANCE: The main manifestation of many neurological and psychiatric disorders in humans is altered behavior. The rich behavioral repertoires exhibited by songbirds make them ideal animal's nriodels in which to mimic human diseases that affect behavior. We propose to develop new molecular tools that will allow for genetic manipulation of songbirds to generate animal models of human diseases that affect complex cognitive functions and communication disorders.

描述（由申请人提供）：几十年来，鸣禽一直是研究与人类健康相关的神经生物学问题的丰富实验系统。特别是，鸣禽是研究声音学习的生物学基础的主要非人类模型，声音学习是语音习得的关键行为基础。此外，鸣禽是研究大脑不对称、大脑发育的激素控制、睡眠的生理功能、大脑性别特异性差异、行为诱导的基因表达和成人神经发生等问题的理想系统。尽管如此，尽管鸣禽对神经生物学很重要，但其作为实验系统的实用性却因缺乏基因操纵方法而受到限制。最近我们成功地将慢病毒介导的转基因应用于斑胸草雀（Agate et al., 2009）。虽然这一成果证明了慢病毒介导的鸣禽转基因的可行性，但目前的方法效率低下、劳动密集型且成本高昂。在本提案中，我们计划优化现有策略并生成新工具来开发实用的鸟类转基因技术，可供其他鸣禽神经生物学实验室使用。对鸣禽进行基因操作的能力将为研究具有强大行为能力的动物物种的基因与大脑功能之间的关系提供无与伦比的机会。转基因鸣禽将使我们能够建立影响复杂认知功能和沟通障碍的人类疾病的动物模型，而这些疾病只能在其他动物物种中进行不完整的建模。公共卫生相关性：人类许多神经和精神疾病的主要表现是行为改变。鸣禽所表现出的丰富的行为能力使它们成为模仿影响行为的人类疾病的理想动物模型。我们建议开发新的分子工具，对鸣禽进行基因操作，以生成影响复杂认知功能和沟通障碍的人类疾病的动物模型。