Characterization of the Transcriptome in an Emerging Model for Social Behavior

描述(由申请人提供)：本申请涉及广泛的挑战领域(01)：行为，行为改变，预防和特定挑战主题，01-GM-102：社会行为研究的模式生物。识别和发展模式生物，以便对社会行为的遗传、生化、生理和环境成分进行综合分析。精神健康障碍，包括自闭症谱系障碍、精神分裂症和抑郁症，部分特征是社会行为的严重损害，包括社会互惠、社会认知和社会动机。不幸的是，由于传统动物模型如小鼠和大鼠的社会能力有限，我们对支配社会行为的遗传和神经生物学机制的了解很少。因此，治疗社会行为缺陷的药物干预收效甚微。然而，草原田鼠(Microtus Ochrogaster)正在迅速崛起，成为了解社会行为基本神经生物学的主要模式生物。与老鼠和大鼠等更成熟的啮齿动物模型相比，田鼠表现出更丰富和多样化的复杂社会行为。例如，社会上一夫一妻制的草原田鼠是高度依附的，与它们的配偶形成终身的配对纽带，父母双方都对它们的幼崽提供广泛的照顾。相比之下，草甸田鼠(M.pennsylvanicus)相对不合群，不形成任何类型的社交依恋，而且是单亲。田鼠物种之间的比较研究已经导致了几个导致社会行为差异的基因和神经通路的确定，然而，很大程度上是因为这些物种缺乏基因组资源，研究一直局限于对少数候选基因的研究。这项研究计划的目标是通过开发一种关键的基因组资源--田鼠基因序列目录，推动草原田鼠作为一种非凡的模式生物的发展，以了解社会行为的生物学基础。具体地说，我们将1)生成18,000个田鼠基因的部分或完整基因序列，这些基因包含50%的转录组；2)首次在全基因组范围内检查社会纽带形成的性质。总而言之，这项研究项目将为人类社会行为的新兴模式提供关键资源，并可能导致发现参与调节复杂社会行为(如社会纽带)的新基因途径。这些发现可能最终导致新的药物干预措施，以增强自闭症、精神分裂症或抑郁症的社会认知功能。 公共卫生相关性：动物模型对于发现社会行为的遗传、生化、生理和环境成分至关重要。这项研究项目的目标是开发一种关键的资源，以开发一种新兴的动物模型系统，该系统已被证明对理解与酒精中毒、自闭症、父母照顾和配对联系有关的人类社会行为的生物学和环境机制是有用的。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (01): Behavior, Behavioral Change, and Prevention and specific Challenge Topic, 01-GM-102: Model organisms for social behavior studies. Identification and development of model organisms that allow for integrative analyses of the genetic, biochemical, physiological, and environmental components of social behavior. Mental health disorders, including autism spectrum disorders, schizophrenia and depression, are characterized in part by severe impairments in social behaviors including social reciprocity, social cognition and social motivation. Unfortunately, because of the limited social repertoire of traditional animal models such as mice and rats, our understanding of the genetic and neurobiological mechanisms that govern social behaviors are poorly understood. Consequently, pharmacological interventions to treat deficits in social behaviors have met with little success. However, the prairie vole (Microtus ochrogaster) is rapidly emerging as a premier model organism for understanding the fundamental neurobiology of social behaviors. In contrast to more established rodent models such as mice and rats, voles demonstrate a much richer and diverse range of complex social behaviors. For instance, socially monogamous prairie voles are highly affiliative, form life-long pair bonds with their mates, and both parents provide extensive care of their young. In contrast, meadow voles (M. pennsylvanicus) are relatively asocial, do not form social attachments of any sort, and are uniparental. Comparative studies between vole species have already led to the identification of several genes and neural pathways that contribute to variation in social behaviors, yet, largely because of a lack of genomic resources for these species, research has been limited to the study of a handful of candidate genes. The goal of this research proposal is to advance the development of the prairie vole as an extraordinary model organism for understanding the biological underpinnings of social behaviors by developing a key genomic resource, a catalog of vole gene sequences. Specifically we will 1) generate partial or complete gene sequences for 18,000 vole genes that encompass > 50% of the transcriptome, and 2) for the first time examine the nature of social bond formation on a genome-wide scale. In summary, this research project will generate a critical resource for an emerging model of human social behavior and will likely lead the discovery of novel gene pathways involved in the regulation of complex social behavior such as social bonding. These discoveries may ultimately lead to novel pharmacological interventions to enhance social cognitive function in autism, schizophrenia, or depression. PUBLIC HEALTH RELEVANCE: Animal models are critical for discovering the genetic, biochemical, physiological and environmental components of social behavior. The goal of this research project is to develop a key resource needed to exploit an emerging animal model system that has proven utility for understanding the biological and environmental mechanisms of social behavior in humans related to alcoholism, autism, parental care, and pair-bonding.