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.
Highlights
Autism spectrum disorder (ASD) encompasses a wide range of neurological disorders with developmental origins, displaying a variety of symptoms and all including the key characteristics of impaired social interaction and excessive repetitive behaviors and/or restricted interests [1]
We showed that mice carrying Methyl-CpG-binding protein 2 (MECP2) duplication had specific defects in spine pruning, while the 15q11-13 duplication mouse model had impaired spine formation
Its lossof-function mutations result in Rett syndrome [32, 33, 39], while its overexpression leads to progressive neurological symptoms with ASD features
Summary
Autism spectrum disorder (ASD) encompasses a wide range of neurological disorders with developmental origins, displaying a variety of symptoms and all including the key characteristics of impaired social interaction and excessive repetitive behaviors and/or restricted interests [1]. These behavioral abnormalities are thought to be caused by alterations in neural circuits. Based on accumulating evidence demonstrating defects in synaptic development and/or function in animal models of ASD and in patients, autism has been considered as the disease of synapse [2,3,4,5,6,7]. Spines undergo dramatic changes during development, in species ranging from rodents to humans [12,13,14,15,16,17,18,19]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.