Investigating the role of CNTNAP2 gene in vocal learning in mutant songbirds

研究 CNTNAP2 基因在突变鸣禽声音学习中的作用

基本信息

批准号：
8529590
负责人：
CARLOS LOIS
金额：
$ 19.76万
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：
2012
资助国家：
美国
起止时间：
2012-08-13 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8529590
关键词：
Acute Adolescent Affect Anatomy Animal Model Animals Area Autistic Disorder Behavior Behavioral Birds Boxing Brain Cell Nucleus Communication Communication impairment Development Disease Dissection Down-Regulation Exhibits Genes Genetic Genetic Engineering Hearing Human Impairment Laboratories Language Language Development Lead Learning Lentivirus Vector Link Maps Mediating Memory Messenger RNA Methods Modeling Modification Molecular Mutation Neurodevelopmental Disorder Pathway interactions Patients Performance Play Predisposition Production Property Proteins RNA Interference Research Research Personnel Role Series Signal Transduction Songbirds Speech System Transgenic Organisms autism spectrum disorder base communication behavior contactin critical period developmental disease forkhead protein genetic manipulation mutant prevent social specific language impairment tool vocal learning vocalization zebra finch

项目摘要

DESCRIPTION (provided by applicant): Communication impairments are some of the most debilitating consequences of a number of neurodevelopmental disorders, including autism spectrum disorders (ASD). It is thought that the communication impairments associated with neurodevelopmental disorders may be due to the perturbed assembly of brain areas involved in vocal communication. In recent years a number of genes, including the transcription factor FoxP2 and its target CNTNAP2, have been linked to language specific impairments and to ASD in humans, suggesting that they could play a direct role in speech and language acquisition. However, the lack of adequate animal models to specifically study vocal learning and communication has prevented the dissection of the genetic components involved in communication behaviors. Songbirds are currently the best animal model to study vocal communication because song learning in these animals shares critical features with speech acquisition in humans. Moreover, songbirds have a dedicated brain circuit that is required for the learning and production of vocal signals. Finally, both Foxp2 and CNTNAP2 are expressed in the song system suggesting that speech acquisition in humans and song learning in songbirds involves similar molecular pathways. Thus, songbirds could be an excellent model to study the genetic basis of communication-related aspects of neurodevelopmental disorders, as they represent the ideal system to study how genes orchestrate the assembly of a brain circuit dedicated to vocal learning and production. Our laboratory has developed new methods for the genetic modification of songbirds that will enable us and other researchers to generate genetic animal models for vocal communication disorders. In this proposal we describe a plan to generate genetically-engineered songbirds deficient in CNTNAP2, which will open a new avenue for investigating the role of genes on the assembly and function of the brain circuits involved in vocal communication. This approach should lead to a better understanding on how mutations in this and other genes result in communication deficits such as the ones observed in patients with ASD and other neurodevelopmental disorders.

描述（由申请人提供）：沟通障碍是许多神经发育障碍（包括自闭症谱系障碍（ASD））的最令人衰弱的后果。人们认为，与神经发育障碍相关的沟通障碍可能是由于涉及声音交流的大脑区域的干扰。近年来，包括转录因子FOXP2及其目标CNTNAP2在内的许多基因与语言特定的障碍和人类的ASD有关，这表明它们可以在语音和语言获取中发挥直接作用。然而，缺乏足够的动物模型来专门研究声音学习和交流，这阻止了对沟通行为涉及的遗传成分的解剖。鸣禽目前是研究声音交流的最佳动物模型，因为这些动物中的歌曲学习与人类的语音获取具有关键特征。此外，鸣禽具有专用的大脑电路，这是人声信号的学习和生产所需的。最后，FOXP2和CNTNAP2都在歌曲系统中表达，这表明人类的语音获取和鸣禽中的歌曲学习涉及相似的分子途径。因此，鸣禽可能是研究神经发育障碍与沟通相关方面的遗传基础的绝佳模型，因为它们代表了研究基因如何策划专用于声音学习和生产的脑电路的理想系统。我们的实验室开发了新的方法来修饰鸣禽，这将使我们和其他研究人员能够为人声交流障碍生成遗传动物模型。在此提案中，我们描述了一项计划，该计划生成了CNTNAP2中缺陷遗传学的鸣禽，该鸟将开辟一条新的途径，以研究基因在涉及声音交流中脑电路的组装和功能中的作用。这种方法应该更好地了解该基因和其他基因中的突变如何导致沟通缺陷，例如在ASD和其他神经发育障碍患者中观察到的突变。