Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.
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DOI：
10.1038/nature09965
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发表时间：
2011-04-28
期刊：
影响因子：
64.8
通讯作者：
Feng, Guoping
中科院分区：
文献类型：
--
作者：
Peca, Joao;Feliciano, Catia;Ting, Jonathan T.;Wang, Wenting;Wells, Michael F.;Venkatraman, Talaignair N.;Lascola, Christopher D.;Fu, Zhanyan;Feng, Guoping
自闭症谱系障碍（ASD）包括一系列障碍，这些障碍都以神经行为缺陷为核心，其特征是社交互动普遍异常、沟通缺陷以及兴趣受限和重复行为。这些异常行为背后的神经学基础和电路机制知之甚少。Shank3是一种突触后蛋白，其在遗传水平上的破坏被认为是导致22q13缺失综合征（McDermid综合征）和其他非综合征性ASD的发展的原因。在这里，我们发现Shank3基因缺失的小鼠表现出自我伤害的重复梳理和社会互动的缺陷。细胞，电生理和生化分析发现缺陷的纹状体突触和皮质纹状体电路在Shank3突变小鼠。我们的研究结果证明了Shank3在神经元连接的正常发育中的关键作用，并建立了Shank3基因中断与小鼠自闭症样行为发生之间的因果关系。
Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. Shank3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for development of 22q13 deletion syndrome (Phelan-McDermid Syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for Shank3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic like-behaviours in mice.
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影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
DOI：
10.1083/jcb.136.3.669
发表时间：
1997-02-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim E;Naisbitt S;Hsueh YP;Rao A;Rothschild A;Craig AM;Sheng M
通讯作者：
Sheng M
影响因子：
5.3
作者：
Hung, Albert Y.;Futai, Kensuke;Sheng, Morgan
通讯作者：
Sheng, Morgan
DOI：
10.1001/archpediatrics.2009.98
发表时间：
2009-10-01
影响因子：
--
作者：
Rosenberg, Rebecca E.;Law, J. Kiely;Law, Paul A.
通讯作者：
Law, Paul A.
影响因子：
2.5
作者：
McFarlane, H. G.;Kusek, G. K.;Crawley, J. N.
通讯作者：
Crawley, J. N.