ArticleCurrent biology : CB2015
Ube3a imprinting impairs circadian robustness in Angelman syndrome models.
Article in Current biology : CB, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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51 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Meta-analysis of transcriptomic datasets identifies genes enriched in the mammalian circadian pacemaker.Nucleic acids research · 2017Pooled it
- Operant behavior is reliably impaired in a mouse model of Angelman syndrome.Research square · 2026Article
- Co-designing Nova Sleepcare: identifying priority areas for implementation.Frontiers in pediatrics · 2026Article
- Mouse model of Angelman syndrome exhibits reduced retinal activity during development.Frontiers in neuroscience · 2026Article
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- A preclinical pig model of Angelman syndrome mirrors the early developmental trajectory of the human condition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Use of Basket Trials to Solve Sleep Problems in Patients with Rare Diseases.Clocks & sleep · 2024Article
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- Do metabolic deficits contribute to sleep disruption in monogenic intellectual disability syndromes?Trends in neurosciences · 2024Review
- A clinical-translational review of sleep problems in neurodevelopmental disabilities.Journal of neurodevelopmental disorders · 2024Review
- Sleep disturbance in Angelman syndrome patients.Orphanet journal of rare diseases · 2024Review
- UBE3A: The Role in Autism Spectrum Disorders (ASDs) and a Potential Candidate for Biomarker Studies and Designing Therapeutic Strategies.Diseases (Basel, Switzerland) · 2023Review
- Hyperphagia, Growth, and Puberty in Children with Angelman Syndrome.Journal of clinical medicine · 2023Article
- A cryptic microdeletion del(12)(p11.21p11.23) within an unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.Scientific reports · 2023Article
- A microdeletion del(12)(p11.21p11.23) with a cryptic unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.Research square · 2023Article
- The Hippocampal Response to Acute Corticosterone Elevation Is Altered in a Mouse Model for Angelman Syndrome.International journal of molecular sciences · 2022Article
- Death of a Protein: The Role of E3 Ubiquitin Ligases in Circadian Rhythms of Mice and Flies.International journal of molecular sciences · 2022Review
- Circadian Rhythms and Sleep Are Dependent Upon Expression Levels of Key Ubiquitin LigaseFrontiers in behavioral neuroscience · 2022Article
- Dissociating motor impairment from five-choice serial reaction time task performance in a mouse model of Angelman syndrome.Frontiers in behavioral neuroscience · 2022Article
- Dysregulated CRMP Mediates Circadian Deficits in a Drosophila Model of Fragile X Syndrome.Neuroscience bulletin · 2021Article
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4 authors at 1 institution in 1 country.
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Abstract
backgroundThe paternal allele of Ube3a is silenced by imprinting in neurons, and Angelman syndrome (AS) is a disorder arising from a deletion or mutation of the maternal Ube3a allele, which thereby eliminates Ube3a neuronal expression. Sleep disorders such as short sleep duration and increased sleep onset latency are very common in AS.
resultsWe found a unique link between neuronal imprinting of Ube3a and circadian rhythms in two mouse models of AS, including enfeebled circadian activity behavior and slowed molecular rhythms in ex vivo brain tissues. As a consequence of compromised circadian behavior, metabolic homeostasis is also disrupted in AS mice. Unsilencing the paternal Ube3a allele restores functional circadian periodicity in neurons deficient in maternal Ube3a but does not affect periodicity in peripheral tissues that are not imprinted for uniparental Ube3a expression. The ubiquitin ligase encoded by Ube3a interacts with the central clock components BMAL1 and BMAL2. Moreover, inactivation of Ube3a expression elevates BMAL1 levels in brain regions that control circadian behavior of AS-model mice, indicating an important role for Ube3a in modulating BMAL1 turnover.
conclusionsUbe3a expression constitutes a direct mechanistic connection between symptoms of a human neurological disorder and the central circadian clock mechanism. The lengthened circadian period leads to delayed phase, which could explain the short sleep duration and increased sleep onset latency of AS subjects. Moreover, we report the pharmacological rescue of an AS phenotype, in this case, altered circadian period. These findings reveal potential treatments for sleep disorders in AS patients.
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