Moy Sheryl S, Nadler Jessica J, Young Nancy B, Perez Antonio, Holloway L Paige, Barbaro Ryan P, Barbaro Justin R, Wilson Lindsay M, Threadgill David W, Lauder Jean M, Magnuson Terry R, Crawley Jacqueline N
North Carolina STAART Center for Autism Research, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Behav Brain Res. 2007 Jan 10;176(1):4-20. doi: 10.1016/j.bbr.2006.07.030. Epub 2006 Sep 12.
Three defining clinical symptoms of autism are aberrant reciprocal social interactions, deficits in social communication, and repetitive behaviors, including motor stereotypies and insistence on sameness. We developed a set of behavioral tasks designed to model components of these core symptoms in mice. Male mice from 10 inbred strains were characterized in assays for sociability, preference for social novelty, and reversal of the spatial location of the reinforcer in T-maze and Morris water maze tasks. Six strains, C57BL/6J, C57L/J, DBA/2J, FVB/NJ, C3H/HeJ, and AKR/J, showed significant levels of sociability, while A/J, BALB/cByJ, BTBR T(+)tf/J, and 129S1/SvImJ mice did not. C57BL/6J, C57L/J, DBA/2J, FVB/NJ, BALB/cByJ, and BTBR T(+)tf/J showed significant preference for social novelty, while C3H/HeJ, AKR/J, A/J, and 129S1/SvImJ did not. Normal scores on relevant control measures confirmed general health and physical abilities in all strains, ruling out artifactual explanations for social deficits. Elevated plus maze scores confirmed high anxiety-like behaviors in A/J, BALB/cByJ, and 129S1/SvImJ, which could underlie components of their low social approach. Strains that showed high levels of performance on acquisition of a T-maze task were also able to reach criterion for reversal learning. On the Morris water maze task, DBA/2J, AKR/J, BTBR T(+)tf/J, and 129S1/SvImJ failed to show significant quadrant preference during the reversal probe trial. These results highlight a dissociation between social task performance and reversal learning. BTBR T(+)tf/J is a particularly interesting strain, displaying both low social approach and resistance to change in routine on the water maze, consistent with an autism-like phenotype. Our multitask strategy for modeling symptoms of autism will be useful for investigating targeted and random gene mutations, QTLs, and microarray analyses.
自闭症的三个典型临床症状是异常的相互社交互动、社交沟通缺陷以及重复行为，包括运动刻板行为和对一致性的坚持。我们开发了一套行为任务，旨在模拟小鼠这些核心症状的组成部分。对来自10个近交系的雄性小鼠进行了社交性、对社交新奇性的偏好以及在T迷宫和莫里斯水迷宫任务中强化物空间位置反转的测定。六个品系，即C57BL/6J、C57L/J、DBA/2J、FVB/NJ、C3H/HeJ和AKR/J，表现出显著水平的社交性，而A/J、BALB/cByJ、BTBR T(+)tf/J和129S1/SvImJ小鼠则没有。C57BL/6J、C57L/J、DBA/2J、FVB/NJ、BALB/cByJ和BTBR T(+)tf/J对社交新奇性表现出显著偏好，而C3H/HeJ、AKR/J、A/J和129S1/SvImJ则没有。相关对照测量的正常分数证实了所有品系的总体健康状况和身体能力，排除了社交缺陷的人为解释。高架十字迷宫分数证实了A/J、BALB/cByJ和129S1/SvImJ中存在高度焦虑样行为，这可能是它们社交接近度低的部分原因。在T迷宫任务习得中表现高水平的品系在反转学习中也能够达到标准。在莫里斯水迷宫任务中，DBA/2J、AKR/J、BTBR T(+)tf/J和129S1/SvImJ在反转探测试验期间未表现出显著的象限偏好。这些结果突出了社交任务表现与反转学习之间的分离。BTBR T(+)tf/J是一个特别有趣的品系，在水迷宫中表现出社交接近度低和对日常变化的抵抗，与自闭症样表型一致。我们用于模拟自闭症症状的多任务策略将有助于研究靶向和随机基因突变、数量性状基因座以及微阵列分析。
