Molecular Mechanisms of Social Behavior

项目摘要 多种人类神经系统疾病与社会互动缺陷有关， 通信虽然这些疾病的遗传成分是公认的，但它们的遗传是不确定的。 复杂，疾病位点和受损行为之间的功能联系的识别 被证明是非常困难的。将人类遗传学研究与动物模型研究相结合， 促进建立调节社会行为的全面分子网络的进展， 识别精神障碍中被破坏的基因通路。 本研究的目的是剖析银狐（Vulpes）的遗传行为 vulpes）分解成离散的相互作用的组分，这些组分在分子水平上被理解， 提供了有价值的洞察机制的基础上广泛的哺乳动物互动的社会 行为，包括人类精神疾病。细胞学研究所培育出的狐狸品种 和遗传学（ICG）的俄罗斯科学院表现出显着不同的，遗传决定的 行为表型与典型和非典型人类行为有显著相似之处。现时的建议 是伊利诺伊大学厄巴纳-香槟分校、ICG和 瑞典农业科学大学，以确定这些潜在的分子机制， 行为表型 为了研究这些行为的遗传学，我们将1）识别和比较遗传结构 的攻击性，焦虑相关，并在狐狸亲和行为和2）精细地图狐狸行为位点和定义 参与这些行为调控的候选基因和分子途径。的识别 影响狐狸社会行为的基因座和基因有望提供新的见解， 人类社会行为紊乱的基因。此外，这样一个完善的大型动物模型， 在生物复杂性上介于啮齿类和灵长类之间，可以作为人类和 啮齿动物的行为的分子研究，从而导致潜在的治疗方法的发展。

PROJECT SUMMARY Multiple human neurological disorders are associated with deficits in social interaction and communication. Although a genetic component of these disorders is well established, their inheritance is complex, and the identification of functional connections between disease loci and impaired behaviors has proven to be extremely difficult. Integration of human genetic studies with studies of animal models will facilitate advances in establishing the comprehensive molecular networks that regulate social behaviors and the identification of gene pathways disrupted in mental disorders. The goals of this project are to dissect specific heritable behaviors segregating in the silver fox (Vulpes vulpes) into discrete interacting components that are understood at the molecular level with the intent of providing valuable insights into the mechanisms underlying a broad range of mammalian interactive social behaviors, including human psychiatric disorders. The specific fox strains developed at the Institute of Cytology and Genetics (ICG) of the Russian Academy of Sciences exhibit markedly different, genetically determined behavioral phenotypes with significant parallels to typical and atypical human behaviors. The current proposal is a joint research project between scientists at the University of Illinois at Urbana-Champaign, the ICG, and the Swedish University of Agricultural Sciences to define the molecular mechanisms underlying these behavioral phenotypes. To investigate the genetics of these behaviors we will 1) identify and compare the genetic architecture of aggressive, anxiety-related, and affiliative behaviors in foxes and 2) fine map fox behavioral loci and define candidate genes and molecular pathways involved in the regulation of these behaviors. The identification of loci and genes influencing social behavior in foxes is expected to provide new insights into, and candidate genes for, human disorders of social behavior. Furthermore, such a well-established large animal model, intermediate to rodents and primates in biological complexity, can serve as a bridge between humans and rodents for molecular studies of behavior, thereby leading to the development of potential therapies.