Prkn knockout mice show autistic-like behaviors and aberrant synapse formation

Abstract

SummaryAutism spectrum disorder (ASD) is a neurodevelopmental disorder with high genetic heterogeneity, affecting one in 44 children in the United States. Recent genomic sequencing studies from autistic human individuals indicate that PARK2, a gene that has long been considered in the pathogenesis of Parkinson's disease, is involved in ASD. Here, we report that Prkn knockout (KO) mice demonstrate autistic-like behaviors including impaired social interaction, elevated repetitive behaviors, and deficits in communication. In addition, Prkn KO mice show reduced neuronal activity in the context of sociability in the prelimbic cortex. Cell morphological examination of layer 5 prelimbic cortical neurons shows a reduction in dendritic arborization and spine number. Furthermore, biochemistry and immunocytochemistry analyses reveal alterations in synapse density and the molecular composition of synapses. These findings indicate that Prkn is implicated in brain development and suggest the potential use of the Prkn KO mouse as a model for autism research.