{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:27:35Z","timestamp":1791293255522,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,10,12]],"date-time":"2015-10-12T00:00:00Z","timestamp":1444608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>Methyl\u2010CpG\u2010binding protein 2 (<jats:italic>Mecp2<\/jats:italic>) is an X\u2010linked gene encoding a methylated <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010binding nuclear protein which regulates transcriptional activity. The mutation of <jats:italic><jats:styled-content style=\"fixed-case\">MECP<\/jats:styled-content>2<\/jats:italic> in humans is associated with Rett syndrome (<jats:styled-content style=\"fixed-case\">RTT<\/jats:styled-content>), a neurodevelopmental disorder. Patients with <jats:styled-content style=\"fixed-case\">RTT<\/jats:styled-content> frequently show abnormal sleep patterns and sleep\u2010associated problems, in addition to autistic symptoms, raising the possibility of circadian clock dysfunction in <jats:styled-content style=\"fixed-case\">RTT<\/jats:styled-content>. In this study, we investigated circadian clock function in <jats:italic>Mecp2<\/jats:italic>\u2010deficient mice. We successfully generated both male and female <jats:italic>Mecp2<\/jats:italic>\u2010deficient mice on the wild\u2010type C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 background and <jats:italic><jats:styled-content style=\"fixed-case\">PER<\/jats:styled-content>2<\/jats:italic><jats:sup><jats:italic>Luciferase<\/jats:italic><\/jats:sup> (<jats:italic><jats:styled-content style=\"fixed-case\">PER<\/jats:styled-content>2<\/jats:italic><jats:sup><jats:italic>Luc<\/jats:italic><\/jats:sup>) knock\u2010in background using the clustered regularly interspaced short palindromic repeats (<jats:styled-content style=\"fixed-case\">CRISPR<\/jats:styled-content>)\/Cas9 system. Generated <jats:italic>Mecp2<\/jats:italic>\u2010deficient mice recapitulated reduced activity in mouse models of <jats:styled-content style=\"fixed-case\">RTT<\/jats:styled-content>, and their activity rhythms were diminished in constant dark conditions. Furthermore, real\u2010time bioluminescence imaging showed that the amplitude of <jats:italic><jats:styled-content style=\"fixed-case\">PER<\/jats:styled-content>2<\/jats:italic><jats:sup><jats:italic>Luc<\/jats:italic><\/jats:sup>\u2010driven circadian oscillation was significantly attenuated in <jats:italic>Mecp2<\/jats:italic>\u2010deficient <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content> neurons. On the other hand, <jats:italic>in\u00a0vitro<\/jats:italic> circadian rhythm development assay using <jats:italic>Mecp2<\/jats:italic>\u2010deficient mouse embryonic stem cells (<jats:styled-content style=\"fixed-case\">ESC<\/jats:styled-content>s) did not show amplitude changes of <jats:italic><jats:styled-content style=\"fixed-case\">PER<\/jats:styled-content>2<\/jats:italic><jats:sup><jats:italic>Luc<\/jats:italic><\/jats:sup> bioluminescence rhythms. Together, these results show that <jats:italic>Mecp2<\/jats:italic> deficiency abrogates the circadian pacemaking ability of the <jats:styled-content style=\"fixed-case\">SCN<\/jats:styled-content>, which may be a therapeutic target to treat the sleep problems of patients with <jats:styled-content style=\"fixed-case\">RTT<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/gtc.12305","type":"journal-article","created":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T00:27:52Z","timestamp":1444696072000},"page":"992-1005","source":"Crossref","is-referenced-by-count":35,"title":["Disruption of Me<scp>CP<\/scp>2 attenuates circadian rhythm in <scp>CRISPR<\/scp>\/Cas9\u2010based Rett syndrome model mouse"],"prefix":"10.1111","volume":"20","author":[{"given":"Yoshiki","family":"Tsuchiya","sequence":"first","affiliation":[{"name":"Department of Physiology and Systems Bioscience Kyoto Prefectural University of Medicine Kyoto 602\u20108566 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Physiology and Systems Bioscience Kyoto Prefectural University of Medicine Kyoto 602\u20108566 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Umemura","sequence":"additional","affiliation":[{"name":"Department of Physiology and Systems Bioscience Kyoto Prefectural University of Medicine Kyoto 602\u20108566 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Experiments for Regeneration Institute for Frontier Medical Sciences Kyoto University Kyoto 606\u20108507 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Chronomedicine Hokkaido University Graduate School of Medicine Sapporo 060\u20108638 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Chronobiology Graduate School of Dentistry Osaka University Suita Osaka 565\u20100871 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health Kurume University School of Medicine Kurume 830\u20100011 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sato","family":"Honma","sequence":"additional","affiliation":[{"name":"Department of Chronomedicine Hokkaido University Graduate School of Medicine Sapporo 060\u20108638 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Kondoh","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Experiments for Regeneration Institute for Frontier Medical Sciences Kyoto University Kyoto 606\u20108507 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyojiro","family":"Matsuishi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health Kurume University School of Medicine Kurume 830\u20100011 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Yagita","sequence":"additional","affiliation":[{"name":"Department of Physiology and Systems Bioscience Kyoto Prefectural University of Medicine Kyoto 602\u20108566 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