PDF(Pubmed)
Abstract：
Williams-Beuren syndrome (WBS) is a developmental disorder caused by hemizygous deletion of human chromosome 7q11.23. Hypersocial behavior is one symptom of WBS and contrasts with hyposociality observed in autism spectrum disorder (ASD). Interestingly, duplications of 7q11.23 have been associated with ASD. The social phenotype of WBS has been linked to GTF2I or general transcription factor IIi (TFII-I). Duplication of GTF2I has also been associated with ASD.
We compared mice having either a deletion (Gtf2i+/- ) or duplication (Gtf2i+/dup ) of Gtf2i to wild-type (Gtf2i+/+ ) littermate controls in a series of behavioral tasks including open-field activity monitoring, olfactory probes, a social choice task, social transmission of food preference, habituation-dishabituation, and operant social motivation paradigms.
In open-field observations, Gtf2i+/- and Gtf2i+/dup mice demonstrated normal activity and thigmotaxis, and surprisingly, each strain showed a significant preference for a stimulus mouse that was not observed in Gtf2i+/+ siblings. Both Gtf2i+/- and Gtf2i+/dup mice demonstrated normal olfaction in buried food probes, but the Gtf2i+/- mice spent significantly more time investigating urine scent versus water, which was not observed in the other strains. Gtf2i+/- mice also spent significantly more time in nose-to-nose contact compared to Gtf2i+/+ siblings during the open-field encounter of the social transmission of food preference task. In operant tasks of social motivation, Gtf2i+/- mice made significantly more presses for social rewards than Gtf2i+/+ siblings, while there was no difference in presses for the Gtf2i+/dup mice.
Results were remarkably consistent across testing paradigms supporting a role for GTF2i in the hypersocial phenotype of WBS and more broadly in the regulation of social behavior. Support was not observed for the role of GTF2i in ASD.
We compared mice having either a deletion (Gtf2i+/- ) or duplication (Gtf2i+/dup ) of Gtf2i to wild-type (Gtf2i+/+ ) littermate controls in a series of behavioral tasks including open-field activity monitoring, olfactory probes, a social choice task, social transmission of food preference, habituation-dishabituation, and operant social motivation paradigms.
In open-field observations, Gtf2i+/- and Gtf2i+/dup mice demonstrated normal activity and thigmotaxis, and surprisingly, each strain showed a significant preference for a stimulus mouse that was not observed in Gtf2i+/+ siblings. Both Gtf2i+/- and Gtf2i+/dup mice demonstrated normal olfaction in buried food probes, but the Gtf2i+/- mice spent significantly more time investigating urine scent versus water, which was not observed in the other strains. Gtf2i+/- mice also spent significantly more time in nose-to-nose contact compared to Gtf2i+/+ siblings during the open-field encounter of the social transmission of food preference task. In operant tasks of social motivation, Gtf2i+/- mice made significantly more presses for social rewards than Gtf2i+/+ siblings, while there was no difference in presses for the Gtf2i+/dup mice.
Results were remarkably consistent across testing paradigms supporting a role for GTF2i in the hypersocial phenotype of WBS and more broadly in the regulation of social behavior. Support was not observed for the role of GTF2i in ASD.
摘要：
Williams-Beuren综合征（WBS）是由人类7q11.23染色体半合子缺失引起的发育障碍。超社会行为是WBS的一种症状，与自闭症谱系障碍（ASD）中观察到的低潮形成对比。有趣的是,7q11.23的重复与ASD相关。WBS的社会表型与GTF2I或通用转录因子IIi(TFII-I)相关。GTF2I的复制也与ASD相关。
我们将Gtf2i缺失（Gtf2i+/-）或重复（Gtf2i+/dup）的小鼠与野生型（Gtf2i+/+）同窝动物对照在一系列行为任务中进行了比较，包括野外活动监测。嗅觉探针,社会选择任务，食物偏好的社会传播，习惯性-失意，和有效的社会动机范式。
在开场观测中，Gtf2i+/-和Gtf2i+/dup小鼠表现出正常活动和thigmotaxis，令人惊讶的是，每个品系都显示出对刺激小鼠的显着偏好，而在Gtf2i/兄弟姐妹中未观察到。Gtf2i/-和Gtf2i/dup小鼠在掩埋的食物探针中均表现出正常的嗅觉，但是Gtf2i+/-小鼠花了更多的时间研究尿液气味和水，这在其他菌株中没有观察到。与Gtf2i/兄弟姐妹相比，Gtf2i/-小鼠在食物偏好任务的社会传播的野外相遇中，与Gtf2i/兄弟姐妹相比，在鼻对鼻接触中花费的时间明显更多。在社会动机的运作任务中，Gtf2i+/-小鼠比Gtf2i+/+兄弟姐妹对社会奖励的压力大得多，而Gtf2i+/dup小鼠的压力没有差异。
结果在测试范式中非常一致，支持GTF2i在WBS的超社会表型中以及更广泛地在社会行为调节中的作用。未观察到GTF2i在ASD中的作用的支持。
我们将Gtf2i缺失（Gtf2i+/-）或重复（Gtf2i+/dup）的小鼠与野生型（Gtf2i+/+）同窝动物对照在一系列行为任务中进行了比较，包括野外活动监测。嗅觉探针,社会选择任务，食物偏好的社会传播，习惯性-失意，和有效的社会动机范式。
在开场观测中，Gtf2i+/-和Gtf2i+/dup小鼠表现出正常活动和thigmotaxis，令人惊讶的是，每个品系都显示出对刺激小鼠的显着偏好，而在Gtf2i/兄弟姐妹中未观察到。Gtf2i/-和Gtf2i/dup小鼠在掩埋的食物探针中均表现出正常的嗅觉，但是Gtf2i+/-小鼠花了更多的时间研究尿液气味和水，这在其他菌株中没有观察到。与Gtf2i/兄弟姐妹相比，Gtf2i/-小鼠在食物偏好任务的社会传播的野外相遇中，与Gtf2i/兄弟姐妹相比，在鼻对鼻接触中花费的时间明显更多。在社会动机的运作任务中，Gtf2i+/-小鼠比Gtf2i+/+兄弟姐妹对社会奖励的压力大得多，而Gtf2i+/dup小鼠的压力没有差异。
结果在测试范式中非常一致，支持GTF2i在WBS的超社会表型中以及更广泛地在社会行为调节中的作用。未观察到GTF2i在ASD中的作用的支持。
