Distinct Defects in Spine Formation or Pruning in Two Gene Duplication Mouse Models of Autism.
Distinct Defects in Spine Formation or Pruning in Two Gene Duplication Mouse Models of Autism.
复制标题
两种基因重复自闭症小鼠模型中脊柱形成或修剪的明显缺陷
DOI：
10.1007/s12264-017-0111-8
复制
发表时间：
2017-04
影响因子：
5.6
通讯作者：
Bian WJ
中科院分区：
文献类型：
--
作者：
Wang M;Li H;Takumi T;Qiu Z;Xu X;Yu X;Bian WJ
自闭症谱系障碍（ASD）包括一组复杂的发育性神经障碍，其特征是社交障碍和过度重复行为。近年来，ASD越来越被认为是一种突触疾病。导致ASD的一种主要类型的遗传畸变是基因重复，并且已经产生了几种模拟这些突变的小鼠模型。本文研究了小鼠感觉皮层中MECP 2重复和人类染色体15 q11 -13重复对突触发育和神经回路布线的影响。我们发现，携带MECP 2重复的小鼠在脊柱修剪方面有特定的缺陷，而15 q11 -13重复小鼠模型的脊柱形成受损。我们的研究结果表明，脊柱病理学在自闭症模型之间存在显着差异，并且神经回路发育的不同方面可能针对不同的ASD突变。我们的研究结果进一步强调了基因剂量在大脑正常发育和功能中的重要性。
Autism spectrum disorder (ASD) encompasses a complex set of developmental neurological disorders, characterized by deficits in social communication and excessive repetitive behaviors. In recent years, ASD is increasingly being considered as a disease of the synapse. One main type of genetic aberration leading to ASD is gene duplication, and several mouse models have been generated mimicking these mutations. Here, we studied the effects ofMECP2duplication and human chromosome 15q11-13 duplication on synaptic development and neural circuit wiring in the mouse sensory cortices. We showed that mice carryingMECP2duplication had specific defects in spine pruning, while the 15q11-13 duplication mouse model had impaired spine formation. Our results demonstrate that spine pathology varies significantly between autism models and that distinct aspects of neural circuit development may be targeted in different ASD mutations. Our results further underscore the importance of gene dosage in normal development and function of the brain.