Characterization of a Novel Mouse Model of Restricted Repetitive Behaviors

描述（由申请人提供）：我们最近在近交系 C58/J 小鼠品系中发现了重复运动行为。该菌株强烈地表现出跳跃、翻转和编织等重复行为。 C58/J 小鼠品系在目前使用的限制性重复行为 (RRB) 动物模型中是独一无二的，因为这些异常行为在断奶前自发出现，不需要药物损伤或环境限制（例如隔离饲养）作为触发因素。此外，C58/J 在基因型和表型上与 C57BL/6J 非常相似，允许这种常用的近交系作为适当的对照。这些特性使 C58/J 小鼠品系成为 RRB 研究中潜在的强大动物模型。为了进一步表征 C58/J 小鼠品系作为人类 RRB 模型的特征，我们将使用交叉培养程序来确定母性行为是否有助于 RRB 的出现。此外，我们将确定慢性药物干预对成年 C58/J 小鼠刻板反应的功效。最后，我们将使用磁共振成像确定异常的 RRB 是否与大脑结构变化相关。目前，尚无经过充分验证的 RBB（自闭症核心特征）动物模型。该项目将通过提供小鼠异常行为的神经生物学信息、确定 C58/J 近交株是否确实适合人类 RRB 的临床前筛选，以及加强啮齿动物脑结构成像这一新兴领域，对自闭症谱系障碍研究领域产生积极影响。公共健康相关性：拟议的研究将评估 C58/J 近交小鼠品系作为研究与自闭症相关的受限、重复行为的新型动物模型。目的将确定母亲行为是否会导致新生儿或断奶后期间重复行为的出现，并评估药物对成年 C58/J 小鼠重复行为的功效。最终目标是利用 MRI 技术识别 C58/J 小鼠大脑的结构差异。

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.