{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:34:35Z","timestamp":1791221675654,"version":"4.1.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,11,12]]},"abstract":"<jats:p>To study the pathogenesis of central nervous system abnormalities\n in Down syndrome (DS), we have analyzed a new genetic model of DS, the\n partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of\n the distal aspect of mouse chromosome 16, a segment homologous to human\n chromosome 21 that contains much of the genetic material responsible\n for the DS phenotype. Ts65Dn mice show developmental delay during the\n postnatal period as well as abnormal behaviors in both young and adult\n animals that may be analogous to mental retardation. Though the Ts65Dn\n brain is normal on gross examination, there is age-related degeneration\n of septohippocampal cholinergic neurons and astrocytic hypertrophy,\n markers of the Alzheimer disease pathology that is present in elderly\n DS individuals. These findings suggest that Ts65Dn mice may be used to\n study certain developmental and degenerative abnormalities in the DS\n brain.<\/jats:p>","DOI":"10.1073\/pnas.93.23.13333","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"13333-13338","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":391,"title":["Developmental abnormalities and age-related neurodegeneration in a mouse model of\u2009Down\u2009syndrome"],"prefix":"10.1073","volume":"93","author":[{"given":"David\u2009M.","family":"Holtzman","sequence":"first","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Santucci","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Kilbridge","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Chua-Couzens","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u2009J.","family":"Fontana","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott\u2009E.","family":"Daniels","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randolph\u2009M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Alleva","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles\u2009J.","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William\u2009C.","family":"Mobley","sequence":"additional","affiliation":[{"name":"Department of Neurology, Molecular Biology and Pharmacology, and\r the Center for the Study of Nervous System Injury, Washington\r University School of Medicine, 660 South Euclid Avenue, Box 8111, St.\r Louis, MO 63110; Behavioral Pathophysiology Section, Istituto\r Superiore di Sanita, Viale Regina Elena, 299, I-00161, Rome, Italy;\r Roche Bioscience, Department of Neurobiology, Institute of\r Pharmacology, Palo Alto, CA 94304; Department of Neuroscience,\r Genentech Inc., 460 Point San Bruno Boulevard,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,11,12]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511529702"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-3955(16)38548-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2779(1996)2:2<66::AID-MRDD2>3.0.CO;2-V"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410170310"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(88)90075-6"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-109"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-177"},{"key":"e_1_3_2_8_2","first-page":"117","volume-title":"Segmental Trisomy as a Mouse Model for Down Syndrome","author":"Davisson M T","year":"1993","unstructured":"M T Davisson, C Schmidt, R H Reeves, N G Irving, E C Akeson, B S Harris, R T Bronson Segmental Trisomy as a Mouse Model for Down Syndrome, ed C J Epstein (Wiley\u2013Liss, New York), pp. 117\u2013133 (1993)."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)12052-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02361154"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a107462"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-3472(65)90041-2"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00432509"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0892-0362(93)90071-U"},{"key":"e_1_3_2_15_2","unstructured":"Calamandrei G. 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