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Distinct Defects in Spine Formation or Pruning in Two Gene Duplication Mouse Models of Autism
Pages: 143-152
Year: Issue:  2
Journal: Neuroscience Bulletin

Keyword:  AutismAutism spectrum disorderSpineSpine formationSpinogenesisSpine pruningGene duplicationMECP215q11-13 duplication;
Abstract: Autism spectrum disorder(ASD) encompasses a complex set of developmental neurological disorders,characterized by de?cits 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 chromosome15q11-13 duplication on synaptic development and neural circuit wiring in the mouse sensory cortices. We showed that mice carrying MECP2 duplication had speci?c defects in spine pruning, while the 15q11-13 duplication mouse model had impaired spine formation. Our results demonstrate that spine pathology varies signi?cantly 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.
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