Cara Nasello, Lauren A Poppi, Junbing Wu, Tess F Kowalski, Joshua K Thackray, Riley Wang, Angelina Persaud, Mariam Mahboob, Sherry Lin, Rodna Spaseska, C K Johnson, Derek Gordon, Fadel Tissir, Gary A Heiman, Jay A Tischfield, Miriam Bocarsly, Max A Tischfield
UNLABELLED: Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous to human de novo variants in two high-confidence Tourette genes, CELSR3 and WWC1 . Mice with human mutations in Celsr3 and Wwc1 exhibit cognitive and/or sensorimotor behavioral phenotypes consistent with TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition, occur in both male and female Celsr3 TD models...
November 28, 2023: bioRxiv