Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: A potential model of autism spectrum disorder
Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: A potential model of autism spectrum disorder
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DOI：
10.1016/j.bbr.2007.09.009
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发表时间：
2008-03-05
影响因子：
2.7
通讯作者：
Clark, J. David
中科院分区：
文献类型：
--
作者：
DeLorey, Timothy M.;Sahbaie, Peyman;Clark, J. David
目的：GABA(A)受体在导致复杂神经网络的形成及其所支配的行为的发育事件中起着重要的调节作用。本研究的主要目的是评估GABRB3基因缺陷(GABRB3(-/-))小鼠是否表现出异常的社会行为，这是与自闭症谱系障碍相关的核心缺陷。方法：评估GABRB3(-/-)、窝仔(GABRB3(-/-))和祖系C57BL/6J和129/SVJ的社会和探索行为以及非选择性注意。此外，对GABRB3(-/-)和GABRB3-/-小鼠进行了小脑顶叶大小的半定量评估。结果：与对照组相比，GABRB3(-/-)小鼠在社交、社交新奇和筑巢等与社会行为相关的活动中存在显著缺陷。此外，与对照组相比，GABRB3(-/-)小鼠的探索行为也有所不同，养育发作的频率和持续时间也有所减少，这被认为是非选择性注意的指标。与GABRB3(-/-)小鼠相比，GABRB3(-/-)小鼠也表现出明显的小脑蠕虫发育不良。结论：观察到的行为缺陷，特别是社会行为方面的缺陷，增强了GABRB3基因缺陷小鼠作为自闭症谱系障碍模型的面孔有效性。(C)2007 Elsevier B.V.保留所有权利。
Objective: GABA(A) receptors play an important regulatory role in the developmental events leading to the formation of complex neuronal networks and to the behaviors they govern. The primary aim of this study was to assess whether gabrb3 gene deficient (gabrb3(-/-)) mice exhibit abnormal social behavior, a core deficit associated with autism spectrum disorder.Methods: Social and exploratory behaviors along with non-selective attention were assessed in gabrb3(-/-), littermates (gabrb3(-/-)) and progenitor strains, C57BL/6J and 129/SvJ. In addition, semi-quantitative assessments of the size of cerebellar vermal lobules were performed on gabrb3(-/-) and gabrb3-/- mice.Results: Relative to controls, gabrb3(-/-) mice exhibited significant deficits in activities related to social behavior including sociability, social novelty and nesting. In addition, gabrb3(-/-) mice also exhibited differences in exploratory behavior compared to controls, as well as reductions in the frequency and duration of rearing episodes, suggested as being an index of non-selective attention. Gabrb3(-/-) mice also displayed significant hypoplasia of the cerebellar vermis compared to gabrb3(-/-) mice.Conclusions: The observed behavioral deficits, especially regarding social behaviors, strengthens the face validity of the gabrb3 gene deficient mouse as being a model of autism spectrum disorder. (C) 2007 Elsevier B.V. All rights reserved.