Loss of ASD-Related Molecule Caspr2 Affects Colonic Motility in Mice

Gastrointestinal (GI) symptoms are highly prevalent among individuals with autism spectrum disorder (ASD), but the molecular link between ASD and GI dysfunction remains poorly understood. The enteric nervous system (ENS) is critical for normal GI motility and has been shown to be altered in mouse models of ASD and other neurological disorders. Contactin-associated protein-like 2 (Caspr2) is an ASD-related synaptic cell-adhesion molecule necessary for regulating sensory function in the central and peripheral nervous system. In this study, we examine the role of Caspr2 in GI motility by characterizing Caspr2's expression in the ENS and assessing ENS organization and GI function in Caspr2 mutant mice. We find that Caspr2 is predominantly expressed in enteric sensory neurons in both the small intestine and colon. We further assess colonic motility in Caspr2 mutants using an ex-vivo motility monitor and show altered colonic contractions and faster expulsion of artificial pellets. The organization of neurons within the myenteric plexus remains unchanged. Our results suggest a role for enteric sensory neurons in ASD-related GI dysmotility, a finding relevant to consider in the treatment of ASD-related GI symptoms. ### Competing Interest Statement The authors have declared no competing interest.