{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:48:00Z","timestamp":1791978480194,"version":"4.4.0"},"reference-count":34,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":526,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H06095"],"award-info":[{"award-number":["17H06095"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K07144"],"award-info":[{"award-number":["17K07144"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Dysfunction of glucose transporter 1 (GLUT1) proteins causes infantile epilepsy, which is designated as a GLUT1 deficiency syndrome (GLUT1DS; OMIM #606777). Patients with GLUT1DS display varied clinical phenotypes, such as infantile seizures, ataxia, severe mental retardation with learning disabilities, delayed development, hypoglycorrhachia, and other varied symptoms. Glut1Rgsc200 mutant mice mutagenized with N-ethyl-N-nitrosourea (ENU) carry a missense mutation in the Glut1 gene that results in amino acid substitution at the 324th residue of the GLUT1 protein. In this study, these mutants exhibited various phenotypes, including embryonic lethality of homozygotes, a decreased cerebrospinal-fluid glucose value, deficits in contextual learning, a reduction in body size, seizure-like behavior and abnormal electroencephalogram (EEG) patterns. During EEG recording, the abnormality occurred spontaneously, whereas the seizure-like phenotypes were not observed at the same time. In sleep-wake analysis using EEG recording, heterozygotes exhibited a longer duration of wake times and shorter duration of non-rapid eye movement (NREM) sleep time. The shortened period of NREM sleep and prolonged duration of the wake period may resemble the sleep disturbances commonly observed in patients with GLUT1DS and other epilepsy disorders. Interestingly, an in vivo kinetic analysis of glucose utilization by positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose imaging revealed that glucose transportation was reduced, whereas hexokinase activity and glucose metabolism were enhanced. These results indicate that a Glut1Rgsc200 mutant is a useful tool for elucidating the molecular mechanisms of GLUT1DS.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the joint first authors of the paper.<\/jats:p>","DOI":"10.1242\/dmm.038828","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T15:34:04Z","timestamp":1565364844000},"source":"Crossref","is-referenced-by-count":19,"title":["A new mouse model of GLUT1 deficiency syndrome exhibits abnormal sleep-wake patterns and alterations of glucose kinetics in the brain"],"prefix":"10.1242","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-6040","authenticated-orcid":false,"given":"Tamio","family":"Furuse","sequence":"first","affiliation":[{"name":"RIKEN BioResource Research Center 1 Japan Mouse Clinic , , Tsukuba, Ibaraki 305-0074 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Mizuma","sequence":"additional","affiliation":[{"name":"RIKEN Center for Biosystems Dynamics Research 2 Laboratory for Pathophysiological and Health Science , , Kobe, Hyogo 650-0047 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuki","family":"Hirose","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba 3 , Ibaraki 305-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kushida","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 1 Japan Mouse Clinic , , Tsukuba, Ibaraki 305-0074 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuko","family":"Yamada","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 1 Japan Mouse Clinic , , Tsukuba, Ibaraki 305-0074 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Miura","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 1 Japan Mouse Clinic , , Tsukuba, Ibaraki 305-0074 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Masuya","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 4 Resource Advancement Unit, Integrated Bioresource Information Division , , Tsukuba, Ibaraki 305-0074 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Funato","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba 3 , Ibaraki 305-8575 , Japan"},{"name":"School of Medicine 5 Department of Anatomy , , Faculty of Medicine , , Tokyo 143-8540 , Japan"},{"name":"Toho University 5 Department of Anatomy , , Faculty of Medicine , , Tokyo 143-8540 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba 3 , Ibaraki 305-8575 , Japan"},{"name":"Life Science Center for Survival Dynamics (TARA), University of Tsukuba 6 , Ibaraki 305-8575 , Japan"},{"name":"University of Texas Southwestern Medical Center 7 Department of Molecular Genetics , , Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Onoe","sequence":"additional","affiliation":[{"name":"Human Brain Research Center, Kyoto University Graduate School of Medicine 8 , Kyoto 606-8501 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeharu","family":"Wakana","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 1 Japan Mouse Clinic , , Tsukuba, Ibaraki 305-0074 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,9,12]]},"reference":[{"key":"2024061302285347900_DMM038828C1","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.eplepsyres.2014.11.007","article-title":"Topography of brain glucose hypometabolism and epileptic network in glucose transporter 1 deficiency","volume":"110","author":"Akman","year":"2015","journal-title":"Epilepsy Res."},{"key":"2024061302285347900_DMM038828C2","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/S0169-328X(98)00301-5","article-title":"Glut1 and glut3 expression, but not capillary density, is increased by cobalt chloride in rat cerebrum and retina","volume":"64","author":"Badr","year":"1999","journal-title":"Brain Res. 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