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AS is caused by a deficiency in the ubiquitin ligase E3A (Ube3a) gene product, known to play a dual role as both ubiquitin ligase and transcription coactivator. In AS animal models, multiple Ube3a substrates are accumulated in neurons. So far, studies in mouse models have either aimed at re\u2010expressing Ube3a or manipulating downstream signaling pathways. Reintroducing Ube3a in AS mice showed promising results but may have two caveats. First, it may cause an overdosage in the Ube3a expression, which in turn is known to contribute to autism spectrum disorders. Second, in mutation cases, the exogenous Ube3a may have to compete with the mutated endogenous form. Such two caveats left spaces for developing therapies or interventions directed to targets downstream Ube3a. Notably, Ube3a expression is dynamically regulated by neuronal activity and plays a crucial role in synaptic plasticity. The abnormal synaptic plasticity uncovered in AS mice has been frequently rescued, but circuits symptoms like seizure are resistant to treatment. Future investigations are needed to further clarify the function (s) of Ube3a during development. Here I reviewed the recently identified major Ube3a substrates and signaling pathways involved in AS pathology, the Ube3a expression, imprinting and evolution, the AS mouse models that have been generated and inspired therapeutic potentials, and finally proposed some future explorations to better understand the AS pathology.<\/jats:p>","DOI":"10.1002\/jnr.24576","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T04:58:52Z","timestamp":1577077132000},"page":"1162-1173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Towards an understanding of Angelman syndrome in mice studies"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2153-256X","authenticated-orcid":false,"given":"Xin","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Life Science Hong Kong University of Science and Technology Hong Kong 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