A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations
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<sup>492stop</sup> 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.
Authors
- Hongtao Wang (ORCID: https://orcid.org/0000-0002-8066-475X)
- Zi‐Ai Zhu
- Zhi‐Qi Xiong (ORCID: https://orcid.org/0000-0001-7727-8412)
- Huiwen Zhou (ORCID: https://orcid.org/0000-0003-4793-5068)
- Ya Shen (ORCID: https://orcid.org/0000-0002-7656-0245)
- Jiwei Liu (ORCID: https://orcid.org/0000-0002-9538-1015)
- Yuxian Zhang (ORCID: https://orcid.org/0000-0001-7874-469X)
- Feng Xue
Institutions
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Shanghai Mental Health Center (CN)
- ShanghaiTech University (CN)
- Center for Excellence in Brain Science and Intelligence Technology (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Neuroscience Bulletin
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1007/s12264-024-01346-4
- Citations
- 4
- Primary Topic
- Genetics and Neurodevelopmental Disorders
- Type
- article
- Field-Weighted Citation Impact
- 7.27