ArticleThe Journal of clinical investigation2021
Temporal manipulation of Cdkl5 reveals essential postdevelopmental functions and reversible CDKL5 deficiency disorder-related deficits.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Variable expression ofProceedings of the National Academy of Sciences of the United States of America · 2024Pooled it
- Ganaxolone, an approved therapy for CDKL5-deficiency disorder, is an inhibitor of PTP1B.The Journal of biological chemistry · 2026Article
- High-Definition Brain Network (HDBN) Delineation of CDKL5 Deficiency Disorder (CDD) in Genetically Engineered Mice.Biomolecules · 2026Article
- Base editing restores CDKL5 expression and rescues neuronal deficits in a patient-derived model of CDKL5 deficiency disorder.Scientific reports · 2026Article
- KCC2 activation during postnatal development alleviates long-term deficits in CDKL5-deficient mice.Experimental & molecular medicine · 2026Article
- CDKL5 deficiency results in atypical subregion-specific expression of perineuronal nets during mouse visual critical period.Frontiers in neuroscience · 2026Article
- Future Directions for Studying the Potential of Mammalian Dscam in Autism Spectrum Disorder and Alzheimer's Disease: Insights from Dose Sensitivity.Molecular neurobiology · 2025Review
- Excitatory cortical neurons from CDKL5 deficiency disorder patient-derived organoids show early hyperexcitability not identified in neurogenin2 induced neurons.Neurobiology of disease · 2025Article
- Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories.Genetics · 2025Article
- Adult-Onset Deletion of CDKL5 in Forebrain Glutamatergic Neurons Impairs Synaptic Integrity and Behavior in Mice.International journal of molecular sciences · 2025Article
- Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories.bioRxiv : the preprint server for biology · 2025Article
- Single-cell technology grows up: Leveraging high-resolution omics approaches to understand neurodevelopmental disorders.Current opinion in neurobiology · 2025Review
- De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms.American journal of human genetics · 2025Article
- Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal.Cell reports. Medicine · 2025Article
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- Women With Genetic Epilepsies.Neurology. Genetics · 2025Review
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- Article
- AAV-mediated Stambp gene replacement therapy rescues neurological defects in a mouse model of microcephaly-capillary malformation syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Preclinical studies of gene replacement therapy for CDKL5 deficiency disorder.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
CDKL5 deficiency disorder (CDD) is an early onset, neurodevelopmental syndrome associated with pathogenic variants in the X-linked gene encoding cyclin-dependent kinase-like 5 (CDKL5). CDKL5 has been implicated in neuronal synapse maturation, yet its postdevelopmental necessity and the reversibility of CDD-associated impairments remain unknown. We temporally manipulated endogenous Cdkl5 expression in male mice and found that postdevelopmental loss of CDKL5 disrupts numerous behavioral domains, hippocampal circuit communication, and dendritic spine morphology, demonstrating an indispensable role for CDKL5 in the adult brain. Accordingly, restoration of Cdkl5 after the early stages of brain development using a conditional rescue mouse model ameliorated CDD-related behavioral impairments and aberrant NMDA receptor signaling. These findings highlight the requirement of CDKL5 beyond early development, underscore the potential for disease reversal in CDD, and suggest that a broad therapeutic time window exists for potential treatment of CDD-related deficits.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.