摘要：SummaryAutism susceptibility candidate 2(AUTS2), a risk gene for autism spectrum disorders (ASDs), is implicated in telencephalon development. Because AUTS2 is also expressed in the cerebellum where defects have been linked to ASDs, we investigated AUTS2 functions in the cerebellum. AUTS2 is specifically localized in Purkinje cells (PCs) and Golgi cells during postnatal development.Auts2conditional knockout (cKO) mice exhibited smaller and deformed cerebella containing immature-shaped PCs with reduced expression ofCacna1a.Auts2cKO and knock-down experiments implicated AUTS2 participation in elimination and translocation of climbing fiber synapses and restriction of parallel fiber synapse numbers.Auts2cKO mice exhibited behavioral impairments in motor learning and vocal communications. BecauseCacna1ais known to regulate synapse development in PCs, it suggests that AUTS2 is required for PC maturation to elicit normal development of PC synapses and thus the impairment ofAUTS2may cause cerebellar dysfunction related to psychiatric illnesses such as ASDs.Graphical AbstractDisplay OmittedHighlights•Loss ofAuts2leads to the reduction of cerebellar size•AUTS2 promotes the dendritic maturation of Purkinje cells•AUTS2 participates in PF and CF synapse development of Purkinje cells•Auts2cKO mice exhibit the impaired motor learning and vocal communicationsMolecular Neuroscience; Developmental Neuroscience; Cellular Neuroscience
