Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3.
Somatosensory and sensorimotor consequences associated with the heterozygous disruption of the autism candidate gene, Gabrb3.
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DOI：
10.1016/j.bbr.2010.06.032
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发表时间：
2011-01-01
影响因子：
2.7
通讯作者：
Clark, David J.
中科院分区：
文献类型：
--
作者：
DeLorey, Timothy M.;Sahbaie, Peyman;Hashemi, Ezzat;Li, Wen-Wu;Salehi, Ahmad;Clark, David J.
关键词：
自闭症谱系障碍 (ASD) 的诊断基于三个核心特征：社交互动受损、沟通缺陷以及重复或受限的行为模式。在这种背景下，异常的感觉处理尽管普遍存在并且对核心诊断特征产生影响，但很少受到关注。了解这些感觉异常的根源对于制定旨在最大限度地提高自闭症谱系障碍患者的应对能力的干预策略至关重要。因此，我们选择检查 Gabrb3 基因（一种与 ASD 密切相关的基因）杂合的小鼠中是否存在感觉异常。通过声惊吓反射 (PPI) 的前脉冲抑制来评估小鼠的触觉和热敏感性、感觉运动能力（加速旋转任务）和感觉运动门控。所有杂合子在背根神经节、脊髓、全脑和杏仁核中都表现出癫痫易感性增加和 Gabrb3 表达类似的减少。有趣的是，杂合变异体之间在触觉敏感性、热敏感性、感觉运动能力和 PPI 方面存在显着差异，同时网状丘脑核和终纹床核中 Gabrb3 表达也存在差异。这些差异受到杂合子性别以及 Gabrb3 基因是父系还是母系起源的影响。 Gabrb3 的简单单倍体不足不足以解释这些结果，因此可能涉及其他机制。此外，这是首次报告 ASD 小鼠模型出现触觉和热过敏，这两个特征通常与 ASD 相关。
Autism spectrum disorder (ASD) is diagnosed based on three core features: impaired social interactions, deficits in communication and repetitive or restricted behavioral patterns. Against this backdrop, abnormal sensory processing receives little attention despite its prevalence and the impact it exerts on the core diagnostic features. Understanding the source of these sensory abnormalities is paramount to developing intervention strategies aimed at maximizing the coping ability of those with ASD. Consequently, we chose to examine whether sensory abnormalities were present in mice heterozygous for the Gabrb3 gene, a gene strongly associated with ASD. Mice were assessed for tactile and heat sensitivity, sensorimotor competence (accelerating rotarod task) and sensorimotor gating by prepulse inhibition of the acoustic startle reflex (PPI). All heterozygotes exhibited an increase in seizure susceptibility and similar reductions in Gabrb3 expression in the dorsal root ganglia, spinal cord, whole brain and amygdala. Interestingly, significant differences were noted between heterozygous variants in regards to tactile sensitivity, heat sensitivity, sensorimotor competence and PPI along with differences in Gabrb3 expression in the reticular thalamic nucleus and the bed nucleus of stria terminalis. These differences were influenced by the heterozygotes’ gender and whether the Gabrb3 gene was of paternal or maternal origin. These results are not adequately explained by simple haploinsufficiency of Gabrb3, therefore, additional mechanisms are likely to be involved. In addition, this is the first report of the occurrence of tactile and heat hypersensitivity in an ASD mouse model, two features often associated with ASD.
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影响因子：
3.9
作者：
Cascio, Carissa;McGlone, Francis;Essick, Gregory
通讯作者：
Essick, Gregory
DOI：
10.1073/pnas.96.17.9891
发表时间：
1999-08-17
影响因子：
11.1
作者：
Bonnert, TP;McKernan, RM;Whiting, PJ
通讯作者：
Whiting, PJ
影响因子：
2.7
作者：
DeLorey, Timothy M.;Sahbaie, Peyman;Clark, J. David
通讯作者：
Clark, J. David
影响因子：
6.9
作者：
Fombonne, E
通讯作者：
Fombonne, E
影响因子：
4
作者：
Bittel, DC;Kibiryeva, N;Butler, MG
通讯作者：
Butler, MG