中国科学院脑科学与智能技术卓越创新中心熊志奇研究组发现，一种新的小鼠模型揭示了CDKL5突变缺失中的蛋白质缺陷。相关论文于2025年3月5日发表在《神经科学通报》杂志上。

研究团队引入Cdkl5^492stop小鼠模型，模拟患者的C端截断突变。492stop/Y小鼠表现出改变的树突脊柱形态和自发性癫痫样行为，以及其他行为缺陷。在创建具有各种Cdkl5截断突变的细胞系后，该团队发现这些突变受无义介导的RNA衰变途径的调节。大多数截断突变导致CDKL5蛋白丢失，导致多种疾病表型，并为CDKL5疾病的发病机制提供了新的见解。

据了解，细胞周期蛋白依赖性激酶样5基因（CDKL5）突变是一种严重的神经发育障碍，但截短突变的影响尚不清楚。

附：英文原文

Title: A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations

Author: Feng, Xue, Zhu, Zi-Ai, Wang, Hong-Tao, Zhou, Hui-Wen, Liu, Ji-Wei, Shen, Ya, Zhang, Yu-Xian, Xiong, Zhi-Qi

Issue&Volume: 2025-03-05

Abstract: Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.

DOI: 10.1007/s12264-024-01346-4

Source: https://link.springer.com/article/10.1007/s12264-024-01346-4