Spatial component of: 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. Spatial transcriptomic analyses revealed that Celsr3 mutants featured abnormalities of the extracellular matrix in the striatum. Notably, there are alterations in collagen and extracellular organization. Coronal sections from 4 distinct mice (2 from each group: Celsr3 WT and HZ) from FFPE preserved samples were analyzed by Visium Cytassist近期研究证实，钙粘蛋白EGF LAG七跨膜G型受体3（cadherin EGF LAG sevenpass-Gtype receptor 3，简称CELSR3）基因是抽动障碍（tic disorders, TD）的高置信度风险因子。CELSR3突变小鼠表现出类抽动的刻板理毛行为、抽搐动作，以及感觉运动门控缺陷，此类异常表型可通过抽动障碍治疗手段得到改善。空间转录组分析显示，CELSR3突变小鼠的纹状体细胞外基质存在异常；值得注意的是，其胶原成分与细胞外组织结构均发生改变。本研究采用Visium Cytassist技术，对4只独立小鼠的福尔马林固定石蜡包埋（Formalin-Fixed Paraffin-Embedded, FFPE）样本冠状切片开展分析，每组（CELSR3野生型与杂合型）各包含2只小鼠。