Brain specific Lamellipodin knockout results in hyperactivity and increased anxiety of mice.

Brain specific Lamellipodin knockout results in hyperactivity and increased anxiety of mice.
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脑特异性层状蛋白敲除导致小鼠的多动症和焦虑增加。

DOI:
10.1038/s41598-017-05043-3
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发表时间:
2017-07-14
期刊:
影响因子:
4.6
通讯作者:
Krause M
Krause M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bodo C;Fernandes C;Krause M

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LPD是生长因子和轴突导向受体下游的重要信号整合子。在机制上,LPD通过与F-肌动蛋白、肌动蛋白效应物Ena/Vasp蛋白和SCAR/WAVE复合体相互作用来促进肌动蛋白聚合。因此,LPD支持片状脂虫突起、细胞迁移和内吞作用。在哺乳动物中枢神经系统中,LPD有助于神经元的形态发生和发育过程中的神经元迁移,其线虫同源基因MIG-10也支持突触发生。然而,中枢神经系统LPD缺失对行为的影响尚不清楚。在我们目前的研究中,我们将LPD条件基因敲除小鼠与在CNS特异性Nestin启动子下表达Cre的小鼠系杂交,以限制LPD对中枢神经系统的遗传消融。对由此产生的Nestin-Cre-LPD基因敲除小鼠的详细行为分析揭示了一种特定的行为表型,其特征是多动和焦虑增加。
Lamellipodin (Lpd) functions as an important signalling integrator downstream of growth factor and axon guidance receptors. Mechanistically, Lpd promotes actin polymerization by interacting with F-actin and the actin effectors Ena/VASP proteins and the SCAR/WAVE complex. Thereby, Lpd supports lamellipodia protrusion, cell migration and endocytosis. In the mammalian central nervous system, Lpd contributes to neuronal morphogenesis, neuronal migration during development and its C. elegans orthologue MIG-10 also supports synaptogenesis. However, the consequences of loss of Lpd in the CNS on behaviour are unknown. In our current study, we crossed our Lpd conditional knockout mice with a mouse line expressing Cre under the CNS specific Nestin promoter to restrict the genetic ablation of Lpd to the central nervous system. Detailed behavioural analysis of the resulting Nestin-Cre-Lpd knockout mouse line revealed a specific behavioural phenotype characterised by hyperactivity and increased anxiety.
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