Department of Psychology, and Békésy Laboratory of Neurobiology, Pacific Biosciences Research Center, University of Hawaii at Manoa, 1993 East-West Road, Honolulu, HI 96822, USA.
Genes Brain Behav. 2011 Mar;10(2):228-35. doi: 10.1111/j.1601-183X.2010.00659.x. Epub 2010 Nov 4.
The BTBR T+tf/J inbred mouse strain displays a variety of persistent phenotypic alterations similar to those exhibited in autism spectrum disorders (ASDs). The unique genetic background of the BTBR strain is thought to underlie its lack of reciprocal social interactions, elevated repetitive self-directed grooming, and restricted exploratory behaviors. In order to clarify the existence, range, and mechanisms of abnormal repetitive behaviors within BTBR mice, we performed detailed analyses of the microstructure of self-grooming patterns and noted increased overall grooming, higher percentages of interruptions in grooming bouts and a concomitant decrease in the proportion of incorrect sequence transitions compared to C57BL/6J inbred mice. Analyses of active phase home-cage behavior also revealed an increase in stereotypic bar-biting behavior in the BTBR strain relative to B6 mice. Finally, in a novel object investigation task, the BTBR mice exhibited greater baseline preference for specific unfamiliar objects as well as more patterned sequences of sequential investigations of those items. These results suggest that the repetitive, stereotyped behavior patterns of BTBR mice are relatively pervasive and reflect both motor and cognitive mechanisms. Furthermore, other pre-clinical mouse models of ASDs may benefit from these more detailed analyses of stereotypic behavior.
BTBR T+tf/J 近交系小鼠表现出多种持续性表型改变,类似于孤独症谱系障碍(ASD)患者所表现出的改变。BTBR 系的独特遗传背景被认为是其缺乏相互社交互动、过度重复的自我导向梳理行为以及受限的探索性行为的基础。为了阐明 BTBR 小鼠异常重复行为的存在、范围和机制,我们对自我梳理模式的微观结构进行了详细分析,并注意到与 C57BL/6J 近交系小鼠相比,BTBR 小鼠的整体梳理次数增加,梳理回合中断的百分比更高,且不正确序列转换的比例相应降低。对活动期笼内行为的分析还显示,BTBR 系的刻板的啃咬棒行为相对于 B6 小鼠增加。最后,在新物体探查任务中,BTBR 小鼠对特定的不熟悉物体表现出更大的基线偏好,以及对这些物体进行顺序探查的更有规律的序列。这些结果表明,BTBR 小鼠的重复、刻板的行为模式相对普遍,反映了运动和认知机制。此外,其他 ASD 的临床前小鼠模型可能受益于对刻板行为的这些更详细的分析。