Characterization of a Novel Mouse Model of Restricted Repetitive Behaviors

限制性重复行为的新型小鼠模型的表征

• 批准号: 7799957
• 负责人: SHERYL S MOY
• 金额: $ 22.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-06 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7799957
• 关键词: Acute; Adult; Amygdaloid structure; Animal Model; Antipsychotic Agents; Area; Autistic Disorder; Basal Ganglia; Behavior; Brain; Brain imaging; Brain region; C58/J Mouse; Cerebellum; Characteristics; Chronic; Data; Fluoxetine; Fostering; Frequencies; Future; Genetic; Goals; Haloperidol; Housing; Human; Image; Inbred Mouse; Inbred Strain; Inbred Strains Mice; Individual; Intervention; Laboratories; Life; Magnetic Resonance Imaging; Maternal Behavior; Mental disorders; Modeling; Motor; Mouse Strains; Mus; Neonatal; Neurobiology; Obsessive-Compulsive Disorder; Pervasive Development Disorder; Pharmaceutical Preparations; Procedures; Research; Risperidone; Rodent; Selective Serotonin Reuptake Inhibitor; Severities; Stereotyping; Symptoms; Technology; Therapeutic; Therapeutic Effect; Time; Weaning; autism spectrum disorder; base; brain size; design; developmental disease; innovation; mouse model; novel; pre-clinical; public health relevance; response; restrictive repetitive behavior; sex; tool

DESCRIPTION (provided by applicant): We have recently identified repetitive motor behaviors in the inbred C58/J mouse strain. This strain robustly displays repetitive behaviors such as jumping, flipping and weaving. The C58/J mouse strain is unique among currently used animal models for restrictive, repetitive behaviors (RRB) because these aberrant behaviors emerge spontaneously during the pre-weaning period and do not require pharmacological insult or environmental restriction, such as isolate-housing, as a trigger. In addition, C58/J is genotypically and phenotypically very similar to C57BL/6J, allowing this commonly used inbred strain to serve as an appropriate control. These characteristics make the C58/J mouse strain a potentially powerful animal model in the study of RRB. In order to further characterize the C58/J mouse strain as a model for RRB in humans, we will use a cross-fostering procedure to establish whether maternal behavior contributes to the emergence of RRB. Additionally, we will determine the efficacy of chronic pharmacological intervention on stereotyped responses in adult C58/J mice. Lastly, we will determine whether aberrant RRB is associated with structural changes in brain, using magnetic resonance imaging. At the present time, there are no well- validated animal models of RBB, a core feature of autism. This project will positively impact the field of autism spectrum disorder research by providing information on the neurobiology of aberrant behaviors in mice and by identifying whether the C58/J inbred strain is indeed an appropriate pre-clinical screen for human RRB, as well as strengthening the emerging field of brain structural imaging in rodents. PUBLIC HEALTH RELEVANCE: The proposed studies will evaluate the C58/J inbred mouse strain as a novel animal model for the study of restricted, repetitive behaviors relevant to autism. The aims will determine whether maternal behavior contributes to the emergence of repetitive behaviors during the neonatal or post-weaning period, and evaluate the efficacy of pharmacological agents against repetitive behaviors in adult C58/J mice. The final goal is to identify structural differences in the brains of C58/J mice using MRI technology.

描述（由申请人提供）：我们最近在近交C58/J小鼠菌株中确定了重复的运动行为。这种菌株坚固地显示出重复的行为，例如跳跃，翻转和编织。 C58/J小鼠菌株在当前使用的动物模型中是限制性重复行为（RRB）的独特之处，因为这些异常行为在预断压期间自发出现，并且不需要药理损害或环境限制，例如孤立隔离，例如孤立房屋。此外，C58/J在基因型和表型上与C57BL/6J非常相似，从而使这种常用的近交菌株可作为适当的对照。这些特征使C58/J小鼠菌株成为RRB研究中潜在强大的动物模型。为了进一步将C58/J小鼠菌株作为人类RRB的模型，我们将使用交叉促进程序来确定母体行为是否有助于RRB的出现。此外，我们将确定慢性药理学干预对成年C58/J小鼠刻板印象的疗效。最后，我们将使用磁共振成像确定异常RRB是否与大脑的结构变化有关。目前，RBB的动物模型尚无验证的动物模型，RBB是自闭症的核心特征。该项目将通过提供有关小鼠异常行为的神经生物学的信息，并确定C58/J Inbred菌株是否确实是人类RRB的适当临床前筛选，并增强RODENTS大脑结构成像的出现领域，从而对自闭症谱系障碍研究领域产生积极影响。公共卫生相关性：拟议的研究将评估C58/J近交小鼠菌株，作为研究与自闭症相关的有限重复行为的新型动物模型。目的将确定产妇行为是否有助于新生儿或断奶后重复行为的出现，并评估药理学剂对成人C58/J小鼠的重复行为的疗效。最终的目标是使用MRI技术确定C58/J小鼠大脑的结构差异。