Genetic advances and translational phenotypes in rodent models for Tourette disorder

Tourette disorder (TD) is a neurodevelopmental condition affecting approximately 0.3%-1% of children and adolescents. It is defined by motor and vocal tics but encompasses wide ranging phenotypes due to its complex genetic origins, involving hundreds of risk genes across various signaling pathways. Traditional animal models of TD have focused on circuit manipulation or neuron ablation strategies to investigate its underlying causes and associated brain changes. However, the recent identification of high-confidence risk genes has opened new possibilities for creating models that express the exact genetic variants associated with TD. This review discusses early attempts to model TD in rodents and highlights advancements in next-generation models with true construct validity through the expression of orthologous human mutations in high-confidence risk genes. Additionally, we examine the translational potential of integrating cognitive and sensorimotor approaches to evaluate TD-related phenotypes in rodents, including changes to reinforcement learning, habitual behavior, and incentive motivation.