ArticleThe Journal of clinical investigation2015
Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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Who cites it
155 citing papers in PubMed, 246 citations in OpenAlex.
- Emerging Therapies for Angelman Syndrome.CNS drugs · 2026Review
- A new conditional mouse model for Cre-mediated restoration ofbioRxiv : the preprint server for biology · 2026Article
- Individualized antisense oligonucleotide treatment eligibility of patients living with neurodevelopmental diseases.Cell reports. Medicine · 2026Review
- Genetic Rescue of Disrupted Synaptic Protein Interaction Network Dynamics Following SYNGAP1 Reactivation.Molecular & cellular proteomics : MCP · 2026Article
- Targeting UBE3A and downstream estrogen receptor-β signaling to restore oligodendroglial homeostasis in Angelman syndrome.bioRxiv : the preprint server for biology · 2026Article
- Nickase NmCas9 unsilences paternal Ube3a in a mouse model of Angelman syndrome without causing AAV vector integration.Scientific reports · 2026Article
- Operant behavior is reliably impaired in a mouse model of Angelman syndrome.Research square · 2026Article
- Crossing the finish line towards a disease-modifying treatment for Angelman syndrome.Journal of neurodevelopmental disorders · 2026Review
- A xenotransplantation model for reactivation of paternal UBE3A using human-specific antisense oligonucleotides.Scientific reports · 2026Article
- Multi-targeting zinc finger nuclease vector unsilences paternal UBE3A in a mouse model of Angelman syndrome.Gene therapy · 2026Article
- Cadherin 11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit.Molecular psychiatry · 2026Article
- Juvenile reinstatement of TCF4 in Pitt-Hopkins syndrome model mice reveals a critical window for genetic intervention.bioRxiv : the preprint server for biology · 2025Article
- Genetic rescue of disrupted synaptic protein interaction network dynamics followingbioRxiv : the preprint server for biology · 2025Article
- Ubiquitination in the Nervous System: From Molecular Mechanisms to Disease Implications.Molecular neurobiology · 2025Review
- UBE3A stabilization of β-catenin preserves synaptic proteins essential for motor and cognitive functions in Angelman Syndrome.Molecular autism · 2025Article
- Behavioral and molecular insights into anxiety in ube3a and fmr1 zebrafish models of autism spectrum disorders.Translational psychiatry · 2025Article
- Exploration of a DDX3X Gene Supplementation Therapy Including Expanded Characterization and Novel Findings of Sleep Disturbances inBiological psychiatry global open science · 2025Article
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- AAV-dCas9 vector unsilences paternal Ube3a in neurons by impeding Ube3a-ATS transcription.Communications biology · 2025Article
- Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angelman syndrome (AS) is a severe neurodevelopmental disorder that results from loss of function of the maternal ubiquitin protein ligase E3A (UBE3A) allele. Due to neuron-specific imprinting, the paternal UBE3A copy is silenced. Previous studies in murine models have demonstrated that strategies to activate the paternal Ube3a allele are feasible; however, a recent study showed that pharmacological Ube3a gene reactivation in adulthood failed to rescue the majority of neurocognitive phenotypes in a murine AS model. Here, we performed a systematic study to investigate the possibility that neurocognitive rescue can be achieved by reinstating Ube3a during earlier neurodevelopmental windows. We developed an AS model that allows for temporally controlled Cre-dependent induction of the maternal Ube3a allele and determined that there are distinct neurodevelopmental windows during which Ube3a restoration can rescue AS-relevant phenotypes. Motor deficits were rescued by Ube3a reinstatement in adolescent mice, whereas anxiety, repetitive behavior, and epilepsy were only rescued when Ube3a was reinstated during early development. In contrast, hippocampal synaptic plasticity could be restored at any age. Together, these findings suggest that Ube3a reinstatement early in development may be necessary to prevent or rescue most AS-associated phenotypes and should be considered in future clinical trial design.
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