Rakotomamonjy Jennifer, Davies Devin, Valencia Xavier, Son Olivia, Gomez-Maqueo Ximena, Guemez-Gamboa Alicia
Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA.
Genes (Basel). 2025 Aug 21;16(8):985. doi: 10.3390/genes16080985.
: Protocadherin 7 () belongs to the protocadherin family, the largest subgroup of cell adhesion molecules. Members of this family are highly expressed in the brain, where they serve fundamental roles in many neurodevelopmental processes, including axon guidance, dendrite self-avoidance, and synaptic formation. has been strongly associated with epilepsy in multiple genome-wide association studies (GWAS), as well as with schizophrenia, PTSD, and childhood aggression. Despite these associations, the specific contributions of PCDH7 to epileptogenesis and brain development remain largely unexplored. Most of the existing literature on PCDH7 focuses on its function during cancer progression, with only one study suggesting that PCDH7 regulates dendritic spine morphology and synaptic function via interaction with GluN1. : Here, we generate, validate, and characterize a murine null allele in which a large deletion was introduced by CRISPR. : Analysis of embryonic, postnatal, and adult brain datasets confirmed PCDH7 widespread expression. and mice present no gross morphological defects and normal cortical layer formation. However, a seizure susceptibility assay revealed increased latencies in mice, but not in and mice, potentially explaining the association of PCDH7 with epilepsy. : This initial characterization of null mice suggests that, despite its widespread expression in the CNS and involvement in human epilepsy, PCDH7 is not essential for murine brain development and thus is not a suitable animal model for understanding PCDH7 disruption in humans. However, further detailed analysis of this mouse model may reveal circuit or synaptic abnormalities in null brains.
原钙黏蛋白7（PCDH7）属于原钙黏蛋白家族，是细胞黏附分子中最大的亚群。该家族成员在大脑中高度表达，在许多神经发育过程中发挥着重要作用，包括轴突导向、树突自我回避和突触形成。在多项全基因组关联研究（GWAS）中，PCDH7与癫痫以及精神分裂症、创伤后应激障碍和儿童攻击行为密切相关。尽管存在这些关联，但PCDH7对癫痫发生和大脑发育的具体贡献在很大程度上仍未得到探索。现有的关于PCDH7的大多数文献都集中在其在癌症进展过程中的功能，只有一项研究表明PCDH7通过与GluN1相互作用来调节树突棘形态和突触功能。在此，我们构建、验证并表征了一个小鼠无效等位基因，其中通过CRISPR引入了一个大的缺失。对胚胎期、出生后和成年期大脑数据集的分析证实了PCDH7的广泛表达。PCDH7基因敲除小鼠和杂合子小鼠没有明显形态缺陷，皮质层形成正常。然而，癫痫易感性试验显示PCDH7基因敲除小鼠的潜伏期延长，而杂合子小鼠和野生型小鼠没有，这可能解释了PCDH7与癫痫的关联。对PCDH7基因敲除小鼠的初步表征表明，尽管PCDH7在中枢神经系统中广泛表达并与人类癫痫有关，但其对小鼠大脑发育并非必不可少，因此不是理解人类PCDH7破坏的合适动物模型。然而，对该小鼠模型的进一步详细分析可能会揭示PCDH7基因敲除小鼠大脑中的神经回路或突触异常。
