A role for Agbl4 in regulating social behavior: implications for autism spectrum disorder

초록

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication, along with restricted and repetitive patterns of behavior. ASD arises from diverse neurobiological factors that disrupt brain development, leading to broad impairments in social functioning, language, cognition, emotional regulation, and sensory processing. Recent genetic studies have implicated Agbl4, which encodes cytosolic carboxypeptidase 6 (CCP6), as a potential ASD-associated gene due to its role in tubulin deglutamylation and microtubule regulation. However, the functional significance of Agbl4 in the brain, particularly in regions involved in social behavior such as the medial prefrontal cortex (mPFC), remains largely unknown. In this study, we investigated the behavioral and neurophysiological consequences of Agbl4 deficiency using Agbl4 knockout (KO) mice. Through a multi-modal approach combining behavioral assays, immunohistochemistry, electrophysiological recordings, and transcriptomic analyses, we demonstrate that loss of Agbl4 leads to synaptic and circuit-level disruptions in the mPFC, accompanied by impairments in social behavior.