Shank3-mutant mice lacking exon 9 show altered excitation/inhibition balance, enhanced rearing, and spatial memory deficit.
Shank3-mutant mice lacking exon 9 show altered excitation/inhibition balance, enhanced rearing, and spatial memory deficit.
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DOI：
10.3389/fncel.2015.00094
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发表时间：
2015
影响因子：
5.3
通讯作者：
Kim E
中科院分区：
文献类型：
--
作者：
Lee J;Chung C;Ha S;Lee D;Kim DY;Kim H;Kim E
Shank 3是一种突触后支架蛋白，与突触发育和自闭症谱系障碍有关。已知Shank 3基因产生多种剪接变体，其功能尚未完全探索。在本研究中，我们产生了缺乏Shank 3外显子9的小鼠（Shank 3 Δ9小鼠），因此缺失了10种已知的含有N末端锚蛋白重复区的Shank 3剪接变体中的5种，包括最长的剪接变体Shank 3a。我们的X-gal染色结果显示，Shank 3蛋白编码的外显子9的剪接变体是丰富的上皮层，纹状体，海马，丘脑，但不是在嗅球或小脑，尽管显着的Shank 3 mRNA水平在这些地区。Shank 3 Δ9小鼠的海马CA 1区表现出Schaffer侧支突触的兴奋性传递减少和锥体神经元中自发抑制性突触事件的频率增加。相比之下，内侧前额叶皮层中的前边缘层2/3锥体神经元显示自发抑制性突触事件的频率降低，表明Shank 3 Δ9大脑中兴奋/抑制比率（E/I比率）的改变。这些小鼠在新的环境中表现出轻微的饲养增加和轻微的空间记忆受损，但表现出正常的社会互动和重复行为。这些结果表明，锚蛋白重复包含Shank 3剪接变异体是重要的E/I平衡，饲养行为，和空间记忆。
Shank3 is a postsynaptic scaffolding protein implicated in synapse development and autism spectrum disorders. The Shank3 gene is known to produce diverse splice variants whose functions have not been fully explored. In the present study, we generated mice lacking Shank3 exon 9 (Shank3Δ9 mice), and thus missing five out of 10 known Shank3 splice variants containing the N-terminal ankyrin repeat region, including the longest splice variant, Shank3a. Our X-gal staining results revealed that Shank3 proteins encoded by exon 9-containing splice variants are abundant in upper cortical layers, striatum, hippocampus, and thalamus, but not in the olfactory bulb or cerebellum, despite the significant Shank3 mRNA levels in these regions. The hippocampal CA1 region of Shank3Δ9 mice exhibited reduced excitatory transmission at Schaffer collateral synapses and increased frequency of spontaneous inhibitory synaptic events in pyramidal neurons. In contrast, prelimbic layer 2/3 pyramidal neurons in the medial prefrontal cortex displayed decreased frequency of spontaneous inhibitory synaptic events, indicating alterations in the ratio of excitation/inhibition (E/I ratio) in the Shank3Δ9 brain. These mice displayed a mild increase in rearing in a novel environment and mildly impaired spatial memory, but showed normal social interaction and repetitive behavior. These results suggest that ankyrin repeat-containing Shank3 splice variants are important for E/I balance, rearing behavior, and spatial memory.
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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
影响因子：
6.2
作者：
Bozdagi O;Sakurai T;Papapetrou D;Wang X;Dickstein DL;Takahashi N;Kajiwara Y;Yang M;Katz AM;Scattoni ML;Harris MJ;Saxena R;Silverman JL;Crawley JN;Zhou Q;Hof PR;Buxbaum JD
通讯作者：
Buxbaum JD
影响因子：
4.9
作者：
Gogolla, Nadine;LeBlanc, Jocelyn J.;Quast, Kathleen B.;Sudhof, Thomas C.;Fagiolini, Michela;Hensch, Takao K.
通讯作者：
Hensch, Takao K.
影响因子：
3
作者：
Carbonetto, Salvatore
通讯作者：
Carbonetto, Salvatore
影响因子：
6.2
作者：
Bozdagi O;Tavassoli T;Buxbaum JD
通讯作者：
Buxbaum JD