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

The gene CELSR3 (cadherin EGF LAG sevenpass-Gtype 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基因CELSR3（cadherin EGF LAG七跨膜G型受体3）近日被认定为抽动障碍（tic disorders，TD）的高可信度风险因子。Celsr3突变小鼠可表现出类抽动刻板舔毛行为与肢体抽搐，同时伴随感觉运动门控缺陷（sensorimotor gating deficits），该类异常表型可被抽动障碍治疗手段逆转。单细胞核转录组分析（Single-nucleus transcriptomic analyses）显示，Celsr3突变小鼠存在一群独特的异常纹状体投射神经元（striatal projection neurons）。值得注意的是，编码多巴胺D3受体的Drd3基因（Drd3）在这群细胞以及纹状体基质区D1阳性神经元（striosomal D1-positive neurons）中均显著上调，而在钙视网膜蛋白阳性GABA能中间神经元（calretinin-positive GABAergic interneurons）中则表达下调。本数据集包含来自野生型小鼠与Celsr3杂合子小鼠的快速冷冻剥离的纹状体组织（flash-frozen dissected striatal tissue）的单细胞核RNA测序（single-nuclei RNA sequencing）数据。