CELSR3 deficiency leads to tic-related behaviors and dopaminergic alterations in the striatum

The gene CELSR3 (cadherin EGF LAG seven‐pass-G‐type receptor 3) has been recently recognized as a high-confidence risk factor for tic disorders (TD). Celsr3 mutant mice displayed tic-like grooming stereotypies and jerks, as well as sensorimotor gating deficits, which were opposed by TD therapies. Single-nucleus transcriptomic analyses revealed that Celsr3 mutants featured a unique group of eccentric striatal projection neurons. Notably, the Drd3 gene, encoding the dopamine D3 receptor, was significantly upregulated in these cells as well as striosomal D1-positive neurons, while it was reduced in calretinin-positive GABAergic interneurons. single-nuclei RNA sequencing from flash-frozen dissected striatal tissue from wild-type mice and Celsr3 heterozygous mice