A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations.
10.1007/s12264-024-01346-4
- Author:
Xue FENG
1
;
Zi-Ai ZHU
1
;
Hong-Tao WANG
1
;
Hui-Wen ZHOU
1
;
Ji-Wei LIU
2
;
Ya SHEN
1
;
Yu-Xian ZHANG
1
;
Zhi-Qi XIONG
3
Author Information
1. Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
2. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
3. Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China. xiongzhiqi@ion.ac.cn.
- Publication Type:Journal Article
- Keywords:
Cdkl5;
CDKL5 deficiency disorder;
Nonsense-mediated RNA decay;
Truncating mutations
- MeSH:
Animals;
Disease Models, Animal;
Mice;
Protein Serine-Threonine Kinases/deficiency*;
Mutation/genetics*;
Epileptic Syndromes/genetics*;
Humans;
Dendritic Spines/pathology*;
Spasms, Infantile/genetics*;
Male;
Seizures/genetics*;
Mice, Inbred C57BL
- From:
Neuroscience Bulletin
2025;41(5):805-820
- CountryChina
- Language:English
-
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 Cdkl5492stop 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.
