Moy Sheryl S, Nadler Jessica J, Young Nancy B, Nonneman Randal J, Segall Samantha K, Andrade Gabriela M, Crawley Jacqueline N, Magnuson Terry R
Neurodevelopmental Disorders Research Center, CB#7146, University of North Carolina School of Medicine, Chapel Hill, NC 27599, United States.
Behav Brain Res. 2008 Aug 5;191(1):118-29. doi: 10.1016/j.bbr.2008.03.015. Epub 2008 Mar 21.
Core symptoms of autism include deficits in social interaction, impaired communication, and restricted, repetitive behaviors. The repetitive behavior domain encompasses abnormal motoric stereotypy, an inflexible insistence on sameness, and resistance to change. In recent years, many genetic mouse models of autism and related disorders have been developed, based on candidate genes for disease susceptibility. The present studies are part of an ongoing initiative to develop appropriate behavioral tasks for the evaluation of mouse models relevant to autism. We have previously reported profiles for sociability, preference for social novelty, and resistance to changes in a learned pattern of behavior, as well as other functional domains, for 10 inbred mouse strains of divergent genetic backgrounds. The present studies extend this multi-component behavioral characterization to several additional strains: C58/J, NOD/LtJ, NZB/B1NJ, PL/J, SJL/J, SWR/J, and the wild-derived PERA/EiJ. C58/J, NOD/LtJ, NZB/B1NJ, SJL/J, and PERA/EiJ demonstrated low sociability, measured by time spent in proximity to an unfamiliar conspecific, with 30-60% of mice from these strains showing social avoidance. In the Morris water maze, NZB/B1NJ had a persistent bias for the quadrant where the hidden platform was located during acquisition, even after 9 days of reversal training. A particularly interesting profile was found for C58/J, which had low social preference, poor performance in the T-maze, and overt motoric stereotypy. Overall, this set of tasks and observational methods provides a strategy for evaluating novel mouse models in behavioral domains relevant to the autism phenotype.
自闭症的核心症状包括社交互动缺陷、沟通障碍以及局限的重复行为。重复行为领域包括异常的运动刻板行为、对一致性的固执坚持以及对改变的抗拒。近年来,基于疾病易感性候选基因,已经开发出许多自闭症及相关障碍的基因小鼠模型。本研究是一项正在进行的计划的一部分,该计划旨在开发合适的行为任务,以评估与自闭症相关的小鼠模型。我们之前已经报道了10种具有不同遗传背景的近交系小鼠在社交性、对社交新奇性的偏好、对习得行为模式改变的抗拒以及其他功能领域的表现。本研究将这种多成分行为特征描述扩展到其他几个品系:C58/J、NOD/LtJ、NZB/B1NJ、PL/J、SJL/J、SWR/J以及野生来源的PERA/EiJ。通过与陌生同种个体接近的时间来衡量,C58/J、NOD/LtJ、NZB/B1NJ、SJL/J和PERA/EiJ表现出低社交性,这些品系中30%-60%的小鼠表现出社交回避。在莫里斯水迷宫实验中,NZB/B1NJ在训练阶段对隐藏平台所在象限存在持续偏好,即使在9天的反转训练后依然如此。C58/J表现出特别有趣的行为特征,社交偏好低,在T迷宫实验中表现不佳,且有明显的运动刻板行为。总体而言,这一系列任务和观察方法为评估与自闭症表型相关行为领域的新型小鼠模型提供了一种策略。