DeLorey Timothy M, Sahbaie Peyman, Hashemi Ezzat, Homanics Gregg E, Clark J David
Molecular Research Institute, 1000 Elwell Court, Suite 105, Palo Alto, CA 94303, USA.
Behav Brain Res. 2008 Mar 5;187(2):207-20. doi: 10.1016/j.bbr.2007.09.009. Epub 2007 Sep 14.
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.
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.
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.
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.
γ-氨基丁酸A（GABA(A)）受体在导致复杂神经网络形成及其所调控行为的发育过程中发挥着重要的调节作用。本研究的主要目的是评估γ-氨基丁酸B3（gabrb3）基因缺陷（gabrb3(-/-)）小鼠是否表现出异常社交行为，这是与自闭症谱系障碍相关的核心缺陷。
对gabrb3(-/-)小鼠、同窝小鼠（gabrb3(+/+)）以及亲本品系C57BL/6J和129/SvJ小鼠的社交和探索行为以及非选择性注意力进行评估。此外，对gabrb3(+/+)和gabrb3(-/-)小鼠的小脑蚓部小叶大小进行半定量评估。
与对照组相比，gabrb3(-/-)小鼠在社交行为相关活动中表现出显著缺陷，包括社交能力、社交新奇性和筑巢行为。此外，与对照组相比，gabrb3(-/-)小鼠在探索行为上也表现出差异，并且竖毛发作的频率和持续时间减少，竖毛发作被认为是非选择性注意力的一个指标。与gabrb3(+/+)小鼠相比，gabrb3(-/-)小鼠的小脑蚓部也明显发育不全。
观察到的行为缺陷，尤其是在社交行为方面，增强了gabrb3基因缺陷小鼠作为自闭症谱系障碍模型的表面效度。
