title: Distinct Defects in Spine Formation or Pruning in Two Gene Duplication Mouse Models of Autism.
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.
authors.affiliation: 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.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Child Healthcare, Children's Hospital of Fudan University, Shanghai, 201102, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Li
authors.affiliation: RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takumi
authors.affiliation: 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.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Department of Child Healthcare, Children's Hospital of Fudan University, Shanghai, 201102, China. xuxiu@fudan.edu.cn.
authors.forename: Xiu
authors.initials: X
authors.lastname: Xu
authors.affiliation: 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.|University of Chinese Academy of Sciences, Beijing, 100049, China. yuxiang@ion.ac.cn.|School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. yuxiang@ion.ac.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.affiliation: 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.|University of Chinese Academy of Sciences, Beijing, 100049, China. bwjflame@gmail.com.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Bian
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology*; D002884:Chromosomes, Human, Pair 15; D049229:Dendritic Spines / Q000648:ultrastructure*; D004195:Disease Models, Animal; D020440:Gene Duplication / Q000235:genetics*; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016622:Silver Staining; D013003:Somatosensory Cortex / Q000473:pathology*; D013569:Synapses / Q000648:ultrastructure*
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: 15q11-13 duplication; Autism; Autism spectrum disorder; Gene duplication; MECP2; Spine; Spine formation; Spine pruning; Spinogenesis