ArticleThe Journal of clinical investigation2019
Ube3a reinstatement mitigates epileptogenesis in Angelman syndrome model mice.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- UBE3A isoform-selective and non-selective contributions to Angelman syndrome phenotypes.Molecular psychiatry · 2026Article
- Crossing the finish line towards a disease-modifying treatment for Angelman syndrome.Journal of neurodevelopmental disorders · 2026Review
- Review
- Behavior Decoding Delineates Seizure Microfeatures and Associated Sudden Death Risks in Mouse Models of Epilepsy.Annals of neurology · 2026Article
- Brain-wide Genome Editing via STEP-RNPs for Treatment of Angelman Syndrome.bioRxiv : the preprint server for biology · 2025Article
- Article
- Peptidomimetic inhibitors targeting TrkB/PSD-95 signaling improves cognition and seizure outcomes in an Angelman Syndrome mouse model.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Unraveling the Roles of UBE3A in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2025Review
- Increased expression of chondroitin sulfate proteoglycans in dentate gyrus and amygdala causes postinfectious seizures.Brain : a journal of neurology · 2024Article
- The E3 ubiquitin ligase TRIM9 regulates synaptic function and actin dynamics in response to netrin-1.Molecular biology of the cell · 2024Article
- Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey.Frontiers in neuroanatomy · 2024Article
- UBE3A: The Role in Autism Spectrum Disorders (ASDs) and a Potential Candidate for Biomarker Studies and Designing Therapeutic Strategies.Diseases (Basel, Switzerland) · 2023Review
- Infection-induced epilepsy is caused by increased expression of chondroitin sulfate proteoglycans in hippocampus and amygdala.bioRxiv : the preprint server for biology · 2023Article
- Article
- Stem cell models of Angelman syndrome.Frontiers in cell and developmental biology · 2023Review
- Molecular and behavioral consequences of Ube3a gene overdosage in mice.JCI insight · 2022Article
- AntimiR targeting of microRNA-134 reduces seizures in a mouse model of Angelman syndrome.Molecular therapy. Nucleic acids · 2022Article
- Two siblings suffering from Angelman Syndrome with a novel c.1146T>G mutation in UBE3A: A case report.Biomedical reports · 2022Article
- Animal Models of Epilepsy: A Phenotype-oriented Review.Aging and disease · 2022Review
- Epilepsy and Molecular Phenotype Affect the Neurodevelopment of Pediatric Angelman Syndrome Patients in China.Frontiers in psychiatry · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Angelman syndrome (AS) is a neurodevelopmental disorder in which epilepsy is common (~90%) and often refractory to antiepileptics. AS is caused by mutation of the maternal allele encoding the ubiquitin protein ligase E3A (UBE3A), but it is unclear how this genetic insult confers vulnerability to seizure development and progression (i.e., epileptogenesis). Here, we implemented the flurothyl kindling and retest paradigm in AS model mice to assess epileptogenesis and to gain mechanistic insights owed to loss of maternal Ube3a. AS model mice kindled similarly to wild-type mice, but they displayed a markedly increased sensitivity to flurothyl-, kainic acid-, and hyperthermia-induced seizures measured a month later during retest. Pathological characterization revealed enhanced deposition of perineuronal nets in the dentate gyrus of the hippocampus of AS mice in the absence of overt neuronal loss or mossy fiber sprouting. This pro-epileptogenic phenotype resulted from Ube3a deletion in GABAergic but not glutamatergic neurons, and it was rescued by pancellular reinstatement of Ube3a at postnatal day 21 (P21), but not during adulthood. Our results suggest that epileptogenic susceptibility in AS patients is a consequence of the dysfunctional development of GABAergic circuits, which may be amenable to therapies leveraging juvenile reinstatement of UBE3A.
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