{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:20:23Z","timestamp":1787026823153,"version":"build-2736575974"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>\n                    Normal neurodevelopment requires precise expression of the key ubiquitin ligase gene\n                    <jats:italic>Ube3a<\/jats:italic>\n                    . Comparing newly generated mouse models for\n                    <jats:italic>Ube3a<\/jats:italic>\n                    downregulation (models of Angelman syndrome) vs.\n                    <jats:italic>Ube3a<\/jats:italic>\n                    upregulation (models for autism), we find reciprocal effects of\n                    <jats:italic>Ube3a<\/jats:italic>\n                    gene dosage on phenotypes associated with circadian rhythmicity, including the amount of locomotor activity. Consistent with results from neurons in general, we find that\n                    <jats:italic>Ube3a<\/jats:italic>\n                    is imprinted in neurons of the suprachiasmatic nuclei (SCN), the pacemaking circadian brain locus, despite other claims that SCN neurons were somehow exceptional to these imprinting rules. In addition,\n                    <jats:italic>Ube3a<\/jats:italic>\n                    -deficient mice lack the typical drop in wake late in the dark period and have blunted responses to sleep deprivation. Suppression of physical activity by light in\n                    <jats:italic>Ube3a<\/jats:italic>\n                    -deficient mice is not due to anxiety as measured by behavioral tests and stress hormones; quantification of stress hormones may provide a mechanistic link to sleep alteration and memory deficits caused by\n                    <jats:italic>Ube3a<\/jats:italic>\n                    deficiency, and serve as an easily measurable biomarker for evaluating potential therapeutic treatments for Angelman syndrome. We conclude that reduced\n                    <jats:italic>Ube3a<\/jats:italic>\n                    gene dosage affects not only neurodevelopment but also sleep patterns and circadian rhythms.\n                  <\/jats:p>","DOI":"10.3389\/fnbeh.2022.837523","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T19:53:17Z","timestamp":1648497197000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Circadian Rhythms and Sleep Are Dependent Upon Expression Levels of Key Ubiquitin Ligase Ube3a"],"prefix":"10.3389","volume":"16","author":[{"given":"Shu-qun","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie E.","family":"Mahoney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Houdek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenling","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinming","family":"Zhuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Beaudet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Sumova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Scammell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl Hirschie","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/ng0997-75","article-title":"Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons.","volume":"17","author":"Albrecht","year":"1997","journal-title":"Nat. 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