Dendritic spine pathology in autism: lessons learned from mouse models

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders that affect up to 1.5% of population in the world. Recent large scale genomic studies show that genetic causes of ASD are very heterogeneous. Gene ontology, pathway analysis and animal model studies have revealed several potential converging mechanisms including postsynaptic dysfunction of excitatory synapses. In this review, we focus on the structural and functional specializations of dendritic spines, and describe their defects in ASD. We use Fragile X syndrome, Rett syndrome and Phe-lan-McDermid syndrome, three of the most studied neurodevelopmental disorders with autism features, as examples to demonstrate the significant contribution made by mouse models towards the understanding of monogenic ASD. We envision that the development and application of new technologies to study the function of dendritic spines in valid animal models will eventually lead to innovative treatments for ASD.Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders that affect up to 1.5% of population in the world. Recent large scale genomic studies show that genetic causes of ASD are very heterogeneous. Gene ontology, pathway analysis and animal model studies have revealed several potential converging mechanisms including postsynaptic dysfunction of excitatory synapses. In this review, we focus on the structural and functional specializations of dendritic spines, and describe their defects in ASD. We use Fragile X syndrome, Rett syndrome and Phe-lan-McDermid syndrome, three of the most studied neurodevelopmental disorders with autism features, as examples to demonstrate the significant contribution made by mouse models towards the understanding of monogenic ASD. We envision that the development and application of new technologies to study the function of dendritic spines in valid animal models will eventually lead to innovative treatments for ASD.221-37