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Neurosci Bull. 2017 Apr;33(2):143-152. doi: 10.1007/s12264-017-0111-8. Epub 2017 Mar 3.

Distinct Defects in Spine Formation or Pruning in Two Gene Duplication Mouse Models of Autism.

Wang M1,2, Li H3, Takumi T4, Qiu Z1, Xu X5, Yu X6,7,8, Bian WJ9,10.

Author information

1
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
2
University of Chinese Academy of Sciences, Beijing, 100049, China.
3
Department of Child Healthcare, Children's Hospital of Fudan University, Shanghai, 201102, China.
4
RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan.
5
Department of Child Healthcare, Children's Hospital of Fudan University, Shanghai, 201102, China. xuxiu@fudan.edu.cn.
6
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China. yuxiang@ion.ac.cn.
7
University of Chinese Academy of Sciences, Beijing, 100049, China. yuxiang@ion.ac.cn.
8
School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. yuxiang@ion.ac.cn.
9
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China. bwjflame@gmail.com.
10
University of Chinese Academy of Sciences, Beijing, 100049, China. bwjflame@gmail.com.

Abstract

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 of MECP2 duplication and human chromosome 15q11-13 duplication on synaptic development and neural circuit wiring in the mouse sensory cortices. We showed that mice carrying MECP2 duplication 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.

KEYWORDS:

15q11-13 duplication; Autism; Autism spectrum disorder; Gene duplication; MECP2; Spine; Spine formation; Spine pruning; Spinogenesis

PMID:
28258509
PMCID:
PMC5360848
DOI:
10.1007/s12264-017-0111-8
[Indexed for MEDLINE]
Free PMC Article

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