{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:08:22Z","timestamp":1774645702246,"version":"3.50.1"},"reference-count":44,"publisher":"Proceedings of the National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,5,16]]},"abstract":"<jats:p>\n            About 35% of patients with 22q11 deletion syndrome (22q11DS), which includes DiGeorge and velocardiofacial syndromes, develops psychiatric disorders, mainly schizophrenia and bipolar disorder. We previously reported that mice carrying a multigene deletion (\n            <jats:italic>Df1<\/jats:italic>\n            ) that models 22q11DS have reduced prepulse inhibition (PPI), a behavioral abnormality and schizophrenia endophenotype. Impaired PPI is associated with several psychiatric disorders, including those that occur in 22q11DS, and recently, reduced PPI was reported in children with 22q11DS. Here, we have mapped PPI deficits in a panel of mouse mutants that carry deletions that partially overlap with\n            <jats:italic>Df1<\/jats:italic>\n            and have defined a PPI critical region encompassing four genes. We then used single-gene mutants to identify the causative genes. We show that PPI deficits in\n            <jats:italic>Df1<\/jats:italic>\n            \/+ mice are caused by haploinsufficiency of two genes,\n            <jats:italic>Tbx1<\/jats:italic>\n            and\n            <jats:italic>Gnb1l<\/jats:italic>\n            . Mutation of either gene is sufficient to cause reduced PPI.\n            <jats:italic>Tbx1<\/jats:italic>\n            is a transcription factor, the mutation of which is sufficient to cause most of the physical features of 22q11DS, but the gene had not been previously associated with the behavioral\/psychiatric phenotype. A likely role for\n            <jats:italic>Tbx1<\/jats:italic>\n            haploinsufficiency in psychiatric disease is further suggested by the identification of a family in which the phenotypic features of 22q11DS, including psychiatric disorders, segregate with an inactivating mutation of\n            <jats:italic>TBX1<\/jats:italic>\n            . One family member has Asperger syndrome, an autistic spectrum disorder that is associated with reduced PPI. Thus,\n            <jats:italic>Tbx1<\/jats:italic>\n            and\n            <jats:italic>Gnb1l<\/jats:italic>\n            are strong candidates for psychiatric disease in 22q11DS patients and candidate susceptibility genes for psychiatric disease in the wider population.\n          <\/jats:p>","DOI":"10.1073\/pnas.0600206103","type":"journal-article","created":{"date-parts":[[2006,5,10]],"date-time":"2006-05-10T03:36:15Z","timestamp":1147232175000},"page":"7729-7734","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":290,"title":["<i>Tbx1<\/i>\n            haploinsufficiency is linked to behavioral disorders in mice and humans: Implications for 22q11 deletion syndrome"],"prefix":"10.1073","volume":"103","author":[{"given":"Richard","family":"Paylor","sequence":"first","affiliation":[{"name":"Departments of aMolecular and Human Genetics,"},{"name":"Neuroscience,"}]},{"given":"Beate","family":"Glaser","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;"}]},{"given":"Annalisa","family":"Mupo","sequence":"additional","affiliation":[{"name":"Pediatrics (Cardiology), and"},{"name":"CEINGE Biotecnologie Avanzate and"},{"name":"European School of Molecular Medicine (SEMM), 80145 Naples, Italy;"}]},{"given":"Paris","family":"Ataliotis","sequence":"additional","affiliation":[{"name":"Molecular Medicine Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom;"}]},{"given":"Corinne","family":"Spencer","sequence":"additional","affiliation":[{"name":"Departments of aMolecular and Human Genetics,"},{"name":"Neuroscience,"}]},{"given":"Angela","family":"Sobotka","sequence":"additional","affiliation":[{"name":"Pediatrics (Cardiology), and"}]},{"given":"Chelsey","family":"Sparks","sequence":"additional","affiliation":[{"name":"Pediatrics (Cardiology), and"}]},{"given":"Chul-Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Otolaryngology, Baylor College of Medicine, Houston, TX 77030;"}]},{"given":"John","family":"Oghalai","sequence":"additional","affiliation":[{"name":"Otolaryngology, Baylor College of Medicine, Houston, TX 77030;"}]},{"given":"Sarah","family":"Curran","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, London SE4 8AF, United Kingdom"}]},{"given":"Kieran C.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 9, Ireland; and"}]},{"given":"Stephen","family":"Monks","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 9, Ireland; and"}]},{"given":"Nigel","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;"}]},{"given":"Michael C.","family":"O\u2019Donovan","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;"}]},{"given":"Michael J.","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom;"}]},{"given":"Peter J.","family":"Scambler","sequence":"additional","affiliation":[{"name":"Molecular Medicine Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom;"}]},{"given":"Elizabeth","family":"Lindsay","sequence":"additional","affiliation":[{"name":"Pediatrics (Cardiology), and"},{"name":"CEINGE Biotecnologie Avanzate and"}]}],"member":"341","published-online":{"date-parts":[[2006,5,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-005-5036-9"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200101000-00017"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980710)81:4<328::AID-AJMG10>3.0.CO;2-N"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.56.10.940"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.9.1580"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420131"},{"key":"e_1_3_3_7_2","first-page":"1502","volume":"56","author":"Lindsay E. 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