A Celsr3 Mutation Linked to Tourette Disorder Disrupts Cortical Dendritic Patterning and Striatal Cholinergic Interneuron Excitability.

ABSTRACT: Tourette Disorder (TD) is a prevalent neurodevelopmental condition characterized by chronic motor and vocal tics. A mechanistic understanding of both the genetic etiology and brain pathophysiology remains poor. To gain insight into the molecular underpinnings of TD, we have generated a novel mouse model expressing an orthologous human mutation in CELSR3, a high-confidence TD risk gene. This putative damaging de novo variant, R774H, causes an amino acid substitution within the fifth cadherin repeat. Unlike previous Celsr3 TD models and Celsr3 constitutive null mice, mice homozygous for the R774H amino acid substitution are viable. They have grossly normal forebrain development and no changes to the density of cortical and striatal interneuron subpopulations. However, 3D

SUBMITTER: Nasello C 

PROVIDER: S-EPMC12610430 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature