A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations
Year: 2025
Type: article
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.
Source: Neuroscience Bulletin
Authors: Xue Feng, Zi-Ai Zhu, Hong-Tao Wang, Hui-Wen Zhou, Ji-Wei Liu, Ya Shen, Yu-Xian Zhang, Zhi-Qi Xiong
Institutions: Chinese Academy of Sciences, ShanghaiTech University, Center for Excellence in Brain Science and Intelligence Technology, University of Chinese Academy of Sciences, Shanghai Jiao Tong University, Shanghai Mental Health Center, Shanghai Center for Brain Science and Brain-Inspired Technology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,490
OpenAlex ID: W4408220232