Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Canada.
Faculty of Nursing & Midwifery, Golestan University of Medical Sciences, Gorgan, Iran.
Transl Psychiatry. 2018 Oct 26;8(1):234. doi: 10.1038/s41398-018-0280-x.
Several mouse models of autism spectrum disorder (ASD), including the BTBR T + tf/J (BTBR) inbred strain, display a diverse array of behavioral deficits with particular face validity. Here we propose that phenotyping these preclinical models of ASD should avoid excessive reliance on appearance validity of the behavioral observations. BTBR mice were examined in three non-diagnostic symptoms modalities, beside an anatomical investigation for construct validity. The BTBR strain displayed poor sensorimotor integration as reflected by shorter stride length and greater latency on the balance beam task (BBT) when compared with C57BL/6 (B6) controls. Also, locomotor indices in the open-field task (OFT) revealed that BTBR mice traveled longer distances with a remarkably faster exploration than the B6 group in favor of hyperactivity and impulsiveness. Furthermore, analysis of spatial performance including search strategies in the Morris water task (MWT) indicated spatial impairment in the BTBR strain due to failure to employ spatial strategies during navigation. Quantitative cytoarchitectonics and volumetric examinations also indicated abnormal cortical and subcortical morphology in the BTBR mice. The results are discussed in relation to the neuroanatomical correlates of motor and cognitive impairments in the BTBR strain. We conclude that non-diagnostic autistic-like symptoms in the BTBR mouse strain can be impacted by autism risk factors in a similar way than the traditional diagnostic signs.
几种自闭症谱系障碍（ASD）的小鼠模型，包括 BTBR T + tf/J（BTBR）近交系，表现出一系列具有特殊表面效度的行为缺陷。在这里，我们建议对这些 ASD 的临床前模型进行表型分析时，应避免过度依赖行为观察的表象效度。BTBR 小鼠在三种非诊断症状模式中进行了检查，除了进行解剖学研究以验证结构效度。BTBR 品系在平衡木任务（BBT）中的步幅较短和潜伏期较大，反映出感觉运动整合不良，与 C57BL/6（B6）对照组相比。此外，在旷场任务（OFT）中的运动学指数表明，BTBR 小鼠的行进距离更长，探索速度明显快于 B6 组，表明其过度活跃和冲动。此外，对包括 Morris 水迷宫任务（MWT）中的搜索策略在内的空间性能的分析表明，BTBR 品系的空间性能受损，因为在导航过程中无法采用空间策略。定量细胞构筑学和体积检查也表明 BTBR 小鼠的皮质和皮质下形态异常。结果与 BTBR 品系运动和认知障碍的神经解剖学相关性进行了讨论。我们得出结论，BTBR 小鼠品系中的非诊断性自闭症样症状可能会受到自闭症风险因素的类似影响，就像传统的诊断迹象一样。
