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：
8462635
负责人：
CARLOS LOIS
金额：
$ 30.2万
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/8462635
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 public health relevance 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.

描述（由申请人提供）：鸣禽一直是研究数十年来研究与人类健康相关性的神经生物学问题的丰富实验系统。特别是，鸣禽是研究声乐学习生物学基础的主要非人类模型，这是语音习得的关键行为基板。此外，鸣禽是研究脑不对称性，脑发育的激素控制，睡眠生理功能以及大脑中性别特异性差异，行为诱导的基因表达和成人神经发生的理想系统。尽管如此，尽管缺乏基因操纵方法，但尽管对神经生物学的重要性，但作为实验系统的有用性受到限制。最近，我们成功地将慢病毒介导的转基因应用于斑马雀（Agate等，2009）。尽管这项成就证明了雄鸟鸟类介导的转基因的可行性，但当前的方法效率低下，劳动力较高且昂贵。在此提案中，我们计划优化现有的策略，并生成新颖的工具来开发一种实用的禽类转基因技术，该技术可以由其他鸣禽神经生物学实验室使用。在鸣禽中进行遗传操作的能力将为具有强大的行为库的动物物种中的基因与脑功能之间的关系开放无与伦比的机会。转基因鸣禽将使我们能够产生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建模。