{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T05:29:09Z","timestamp":1792906149844,"version":"4.5.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001695","name":"JST","doi-asserted-by":"publisher","award":["JPMJPF2210"],"award-info":[{"award-number":["JPMJPF2210"]}],"id":[{"id":"10.13039\/501100001695","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI","award":["17H06095"],"award-info":[{"award-number":["17H06095"]}]},{"name":"JSPS KAKENHI","award":["22H04918"],"award-info":[{"award-number":["22H04918"]}]},{"name":"JSPS KAKENHI","award":["22K21351"],"award-info":[{"award-number":["22K21351"]}]},{"name":"JSPS KAKENHI","award":["20H00567"],"award-info":[{"award-number":["20H00567"]}]},{"name":"JSPS KAKENHI","award":["22K19410"],"award-info":[{"award-number":["22K19410"]}]},{"name":"JSPS KAKENHI","award":["24H00671"],"award-info":[{"award-number":["24H00671"]}]},{"name":"JSPS KAKENHI","award":["24H01219"],"award-info":[{"award-number":["24H01219"]}]},{"name":"JSPS KAKENHI","award":["26H00441"],"award-info":[{"award-number":["26H00441"]}]},{"name":"JSPS KAKENHI","award":["26K23580"],"award-info":[{"award-number":["26K23580"]}]},{"name":"JSPS KAKENHI","award":["26507003"],"award-info":[{"award-number":["26507003"]}]},{"name":"World Premier International Research Center Initiative from MEXT to M.Y., AMED","award":["JP21zf0127005"],"award-info":[{"award-number":["JP21zf0127005"]}]},{"name":"World Premier International Research Center Initiative from MEXT to M.Y., AMED","award":["JP21km0908001"],"award-info":[{"award-number":["JP21km0908001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Study Objectives<\/jats:title>\n                    <jats:p>Sleep is regulated by conserved kinase signaling pathways, yet how specific molecular variants encode sleep need, sleep intensity, and circadian timing remains unclear. We investigated the functional specialization of SIK3 isoforms and protein kinase A (PKA)-phosphorylation sites in mouse sleep\/wake and circadian regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We first generated isoform-selective Sik3 knock-in mice expressing either the 150\u00a0kDa or 70\u00a0kDa SIK3 isoform. To determine the isoform-specific effects of the Sleepy (Slp) mutation, which causes exon 13 skipping and deletes a region containing S551, we introduced the mutation separately into the 150\u00a0kDa-specific or 70\u00a0kDa-specific allele. In addition, we generated knock-in mice carrying alanine substitutions at the PKA-phosphorylation sites T469, S551, or S674. Sleep\/wake states were quantified by EEG\/EMG recording, and circadian behavior was assessed by wheel-running under light\u2013dark and constant-dark conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The mouse brain expressed two major SIK3 isoforms: a 150\u00a0kDa isoform and a 70\u00a0kDa isoform generated by intron 14 retention. Isoform-selective knock-in analyses showed that the 150\u00a0kDa isoform was required for normal wakefulness at dark onset and circadian period regulation, whereas the 70\u00a0kDa isoform contributed predominantly to NREM sleep EEG delta power. Introducing the Sleepy mutation into either isoform increased NREM sleep time and delta power. Alanine substitution of T469 or S551, but not S674, produced a Sleepy-like hypersomnia phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Partially separable molecular features of SIK3, including its isoforms and phosphorylation sites, contribute to sleep and circadian regulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/sleep\/zsag244","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:30:00Z","timestamp":1788521400000},"source":"Crossref","is-referenced-by-count":1,"title":["SIK3 isoforms and PKA phosphorylation sites differentially regulate sleep and circadian rhythms"],"prefix":"10.1093","author":[{"given":"Minjeong","family":"Park","sequence":"first","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba 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, Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyo","family":"Kakizaki","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Fujiyama","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Nakata","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-8282","authenticated-orcid":false,"given":"Takato","family":"Honda","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba , Tsukuba ,","place":["Japan"]},{"name":"Medical AI Technologies & Robotics Institute, Xiong\u2019an (MATRIX) , Hebei ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Kanno","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiya","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center in Transborder Medical Research Center, University of Tsukuba , Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center in Transborder Medical Research Center, University of Tsukuba , Tsukuba 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