ArticleNeurobiology of disease2021
X-linked cellular mosaicism underlies age-dependent occurrence of seizure-like events in mouse models of CDKL5 deficiency disorder.
Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Nationwide Survey of Association Between Fever and Epileptic Seizure in CDKL5 Deficiency Disorder Revealed Therapeutic Implications.Annals of clinical and translational neurology · 2026Article
- Ganaxolone, an approved therapy for CDKL5-deficiency disorder, is an inhibitor of PTP1B.The Journal of biological chemistry · 2026Article
- Loss of cyclin-dependent kinase-like 5 results in susceptibility to audiogenic seizures in mice.Epilepsia open · 2026Article
- Safety and efficacy of Igk-TATk-CDKL5 gene therapy in mosaic CDKL5 deficiency.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Pathophysiological Mechanisms Fostering Developmental and Epileptic Encephalopathies (DEE): a Complex Interplay between Genetics, Inflammation and Neurodegeneration.Current neurology and neuroscience reports · 2025Review
- A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations.Neuroscience bulletin · 2025Article
- Article
- Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal.Cell reports. Medicine · 2025Article
- Neuroprotective impact of glycitin on memory impairment in a pentylenetetrazol-induced chronic epileptic rat model: insights into hippocampal histology, oxidative stress, and inflammation.Journal of natural medicines · 2025Article
- A phylogenetic analysis of the CDKL protein family unravels its evolutionary history and supports theFrontiers in cell and developmental biology · 2025Article
- Caregiver Perspective of Benefits and Side Effects of Anti-Seizure Medications in CDKL5 Deficiency Disorder from an International Database.CNS drugs · 2024Article
- CDKL5 sculpts functional callosal connectivity to promote cognitive flexibility.Molecular psychiatry · 2024Article
- Cell type-specific expression, regulation and compensation of CDKL5 activity in mouse brain.Molecular psychiatry · 2024Article
- Overcoming genetic and cellular complexity to study the pathophysiology of X-linked intellectual disabilities.Journal of neurodevelopmental disorders · 2024Review
- Anticonvulsant effect of glycitin in pentylenetetrazol induced male Wistar rat model by targeting oxidative stress and Nrf2/HO-1 signaling.Frontiers in pharmacology · 2024Article
- Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability.Nature communications · 2023Article
- Alzheimer risk-increasing TREM2 variant causes aberrant cortical synapse density and promotes network hyperexcitability in mouse models.Neurobiology of disease · 2023Article
- Loss of CDKL5 Causes Synaptic GABAergic Defects That Can Be Restored with the Neuroactive Steroid Pregnenolone-Methyl-Ether.International journal of molecular sciences · 2022Article
- Flow blockage disrupts cilia-driven fluid transport in the epileptic brain.Acta neuropathologica · 2022Article
- Touchscreen cognitive deficits, hyperexcitability and hyperactivity in males and females using two models of Cdkl5 deficiency.Human molecular genetics · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
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Abstract
CDKL5 deficiency disorder (CDD) is an infantile, epileptic encephalopathy presenting with early-onset seizures, intellectual disability, motor impairment, and autistic features. The disorder has been linked to mutations in the X-linked CDKL5, and mouse models of the disease recapitulate several aspects of CDD symptomology, including learning and memory impairments, motor deficits, and autistic-like features. Although early-onset epilepsy is one of the hallmark features of CDD, evidence of spontaneous seizure activity has only recently been described in Cdkl5-deficient heterozygous female mice, but the etiology, prevalence, and sex-specificity of this phenotype remain unknown. Here, we report the first observation of disturbance-associated seizure-like events in heterozygous female mice across two independent mouse models of CDD: Cdkl5 knockout mice and CDKL5 R59X knock-in mice. We find that both the prevalence and severity of this phenotype increase with aging, with a median onset around 28 weeks of age. Similar seizure-like events are not observed in hemizygous knockout male or homozygous knockout female littermates, suggesting that X-linked cellular mosaicism is a driving factor underlying these seizure-like events. Together, these findings not only contribute to our understanding of the effects of CDKL5 loss on seizure susceptibility, but also document a novel, pre-clinical phenotype for future therapeutic investigation.
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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.