{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:47:37Z","timestamp":1776235657272,"version":"3.50.1"},"reference-count":42,"publisher":"Proceedings of the National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,7,8]]},"abstract":"<jats:p>\n            Phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P\n            <jats:sub>2<\/jats:sub>\n            ] is a signaling phospholipid implicated in a wide variety of cellular functions. At synapses, where normal PtdIns(4,5)P\n            <jats:sub>2<\/jats:sub>\n            balance is required for proper neurotransmission, the phosphoinositide phosphatase synaptojanin 1 is a key regulator of its metabolism. The underlying gene,\n            <jats:italic>SYNJ1<\/jats:italic>\n            , maps to human chromosome 21 and is thus a candidate for involvement in Down's syndrome (DS), a complex disorder resulting from the overexpression of trisomic genes. Here, we show that PtdIns(4,5)P\n            <jats:sub>2<\/jats:sub>\n            metabolism is altered in the brain of Ts65Dn mice, the most commonly used model of DS. This defect is rescued by restoring\n            <jats:italic>Synj1<\/jats:italic>\n            to disomy in Ts65Dn mice and is recapitulated in transgenic mice overexpressing\n            <jats:italic>Synj1<\/jats:italic>\n            from BAC constructs. These transgenic mice also exhibit deficits in performance of the Morris water maze task, suggesting that PtdIns(4,5)P\n            <jats:sub>2<\/jats:sub>\n            dyshomeostasis caused by gene dosage imbalance for\n            <jats:italic>Synj1<\/jats:italic>\n            may contribute to brain dysfunction and cognitive disabilities in DS.\n          <\/jats:p>","DOI":"10.1073\/pnas.0803756105","type":"journal-article","created":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T01:10:47Z","timestamp":1214874647000},"page":"9415-9420","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":149,"title":["Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome"],"prefix":"10.1073","volume":"105","author":[{"given":"Sergey V.","family":"Voronov","sequence":"first","affiliation":[{"name":"*Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032;"}]},{"given":"Samuel G.","family":"Frere","sequence":"additional","affiliation":[{"name":"*Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032;"}]},{"given":"Silvia","family":"Giovedi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, CT 06510;"}]},{"given":"Elizabeth A.","family":"Pollina","sequence":"additional","affiliation":[{"name":"*Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032;"}]},{"given":"Christelle","family":"Borel","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, 1211 Geneva, Switzerland;"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"*Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032;"}]},{"given":"Cecilia","family":"Schmidt","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609;"}]},{"given":"Ellen C.","family":"Akeson","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609;"}]},{"given":"Markus R.","family":"Wenk","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Biological Sciences, The Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260; and"}]},{"given":"Laurent","family":"Cimasoni","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, 1211 Geneva, Switzerland;"}]},{"given":"Ottavio","family":"Arancio","sequence":"additional","affiliation":[{"name":"*Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032;"}]},{"given":"Muriel T.","family":"Davisson","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609;"}]},{"given":"Stylianos E.","family":"Antonarakis","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, 1211 Geneva, Switzerland;"}]},{"given":"Katheleen","family":"Gardiner","sequence":"additional","affiliation":[{"name":"**Department of Pediatrics, Human Medical Genetics Program, University of Colorado Denver, Aurora, CO 80045"}]},{"given":"Pietro","family":"De Camilli","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, CT 06510;"}]},{"given":"Gilbert","family":"Di Paolo","sequence":"additional","affiliation":[{"name":"*Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032;"}]}],"member":"341","published-online":{"date-parts":[[2008,7,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05185"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2005.05.005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81649-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02896"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.3.589"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00644-5"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2892-04.2004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2005.10.004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1525"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.08.005"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30098"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12987-X"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-177"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-006-9056-9"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(03)00769-8"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.2090904"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(01)00405-3"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307813100"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2001.5489"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4621fje"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2100"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181219298"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-17-06788.2003"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.05.022"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/379353a0"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2004.01.012"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200011000-00009"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-006-9129-9"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.44"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-23-09101.2001"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222657399"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.032"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1252"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2001.111.re19"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.7.3841"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1001-927"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.10.169"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(02)00188-3"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04678"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604954103"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.2144\/03356st02"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422831"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0803756105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:32:52Z","timestamp":1649795572000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0803756105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,8]]},"references-count":42,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2008,7,8]]}},"alternative-id":["10.1073\/pnas.0803756105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0803756105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7,8]]},"assertion":[{"value":"2008-03-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-07-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}