{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:40:36Z","timestamp":1793302836050,"version":"4.5.0"},"reference-count":53,"publisher":"Life Science Alliance, LLC","issue":"2","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"crossref","award":["P2022ARZ5J"],"award-info":[{"award-number":["P2022ARZ5J"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"crossref","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"crossref","award":["DBA.AD005.225"],"award-info":[{"award-number":["DBA.AD005.225"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"accepted":{"date-parts":[[2024,11,7]]},"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>\n                    The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes in brain metabolism might contribute to these phenotypes, as many of the deleted genes are involved in metabolic processes, but this is unknown. This study shows for the first time that\n                    <jats:italic>Tbx1<\/jats:italic>\n                    haploinsufficiency causes brain metabolic imbalance. We studied two mouse models of 22q11.2DS using mass spectrometry, nuclear magnetic resonance spectroscopy, and transcriptomics. We found that\n                    <jats:italic>Tbx1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice and\n                    <jats:italic>\n                      Df1\/\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    mice, with a multigenic deletion that includes\n                    <jats:italic>Tbx1<\/jats:italic>\n                    , have elevated brain methylmalonic acid, which is highly brain-toxic. Focusing on\n                    <jats:italic>Tbx1<\/jats:italic>\n                    mutants, we found that they also have a more general brain metabolomic imbalance that affects key metabolic pathways, such as glutamine\u2013glutamate and fatty acid metabolism. We provide transcriptomic evidence of a genotype\u2013vitamin B12 treatment interaction. In addition, vitamin B12 treatment rescued a behavioural anomaly in\n                    <jats:italic>Tbx1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Further studies will be required to establish whether the specific metabolites affected by\n                    <jats:italic>Tbx1<\/jats:italic>\n                    haploinsufficiency are potential biomarkers of brain disease status in 22q11.2DS patients.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202403075","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T11:45:13Z","timestamp":1732103113000},"page":"e202403075","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Brain and behavioural anomalies caused by\n                    <i>Tbx1<\/i>\n                    haploinsufficiency are corrected by vitamin B12"],"prefix":"10.26508","volume":"8","author":[{"given":"Marianna","family":"Caterino","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, Naples, Italy"},{"name":"CEINGE-Biotecnologie Avanzate Franco Salvatore, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Paris","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomolecular Chemistry, National Research Council","place":[", Pozzuoli (Naples), Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Torromino","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR)","place":[", Monterotondo (Rome), Italy"]},{"name":"Department of Humanistic Studies, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6386-2009","authenticated-orcid":true,"given":"Michele","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-2263","authenticated-orcid":true,"given":"Gemma","family":"Flore","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04hadk112","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Genetics and Biophysics","place":[", Naples, Italy"]},{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"of the National Research Council"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabella","family":"Tramice","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomolecular Chemistry, National Research Council","place":[", Pozzuoli (Naples), Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Golini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR)","place":[", Monterotondo (Rome), Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4869-0974","authenticated-orcid":true,"given":"Silvia","family":"Mandillo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR)","place":[", Monterotondo (Rome), Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Cavezza","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR)","place":[", Monterotondo (Rome), Italy"]},{"name":"Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy"},{"name":"PhD Program in Behavioural Neuroscience, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Angelini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Applied Mathematics \u201cMauro Picone,\u201d National Research Council","place":[", Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Ruoppolo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, Naples, Italy"},{"name":"CEINGE-Biotecnologie Avanzate Franco Salvatore, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-658X","authenticated-orcid":true,"given":"Andrea","family":"Motta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biomolecular Chemistry, National Research Council","place":[", Pozzuoli (Naples), Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"De Leonibus","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR)","place":[", Monterotondo (Rome), Italy"]},{"name":"Telethon Institute of Genetics and Medicine, Pozzuoli (Naples), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5330-0256","authenticated-orcid":true,"given":"Antonio","family":"Baldini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9079-9121","authenticated-orcid":true,"given":"Elizabeth","family":"Illingworth","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biology University of Salerno, Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3681-0251","authenticated-orcid":true,"given":"Gabriella","family":"Lania","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04hadk112","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Genetics and Biophysics","place":[", Naples, Italy"]},{"id":[{"id":"https:\/\/ror.org\/04zaypm56","id-type":"ROR","asserted-by":"publisher"}],"name":"of the National Research Council"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"12380","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"2024112008450710000_8.2.e202403075.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.71"},{"key":"2024112008450710000_8.2.e202403075.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600206103"},{"key":"2024112008450710000_8.2.e202403075.3","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201819"},{"key":"2024112008450710000_8.2.e202403075.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091598"},{"key":"2024112008450710000_8.2.e202403075.5","doi-asserted-by":"publisher","DOI":"10.1186\/s40842-019-0087-6"},{"key":"2024112008450710000_8.2.e202403075.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.672360"},{"key":"2024112008450710000_8.2.e202403075.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01859-4"},{"key":"2024112008450710000_8.2.e202403075.8","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-024-02088-0"},{"key":"2024112008450710000_8.2.e202403075.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235651100"},{"key":"2024112008450710000_8.2.e202403075.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.07.027"},{"key":"2024112008450710000_8.2.e202403075.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2010.08.005"},{"key":"2024112008450710000_8.2.e202403075.12","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201600177"},{"key":"2024112008450710000_8.2.e202403075.13","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw267"},{"key":"2024112008450710000_8.2.e202403075.14","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.663598"},{"key":"2024112008450710000_8.2.e202403075.15","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049415"},{"key":"2024112008450710000_8.2.e202403075.16","first-page":"979","article-title":"Vitamin B12 deficiency","volume":"67","author":"Oh","year":"2003","journal-title":"Am Fam Physician"},{"key":"2024112008450710000_8.2.e202403075.17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310533200"},{"key":"2024112008450710000_8.2.e202403075.18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy267"},{"key":"2024112008450710000_8.2.e202403075.19","doi-asserted-by":"publisher","DOI":"10.1038\/43903"},{"key":"2024112008450710000_8.2.e202403075.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.10.025"},{"key":"2024112008450710000_8.2.e202403075.21","doi-asserted-by":"publisher","DOI":"10.1016\/0079-6565(95)01017-3"},{"key":"2024112008450710000_8.2.e202403075.22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1062"},{"key":"2024112008450710000_8.2.e202403075.23","unstructured":"Eriksson L , Byrne T , Johnsson E , Trygg J , Vikstrom C (2013) Basic principles and applications. In Multi- and Megavariate Data Analysis, 3rd edn. Ume\u00e5: Umetrics AB."},{"key":"2024112008450710000_8.2.e202403075.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0491-3"},{"key":"2024112008450710000_8.2.e202403075.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2013.04.008"},{"key":"2024112008450710000_8.2.e202403075.26","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-013-9396-0"},{"key":"2024112008450710000_8.2.e202403075.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2020.02.008"},{"key":"2024112008450710000_8.2.e202403075.28","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23020"},{"key":"2024112008450710000_8.2.e202403075.29","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-022-01236-1"},{"key":"2024112008450710000_8.2.e202403075.30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113598"},{"key":"2024112008450710000_8.2.e202403075.31","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15053"},{"key":"2024112008450710000_8.2.e202403075.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00553-z"},{"key":"2024112008450710000_8.2.e202403075.33","doi-asserted-by":"publisher","DOI":"10.3390\/nu14142825"},{"key":"2024112008450710000_8.2.e202403075.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2017.02.005"},{"key":"2024112008450710000_8.2.e202403075.35","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sby011"},{"key":"2024112008450710000_8.2.e202403075.36","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00469"},{"key":"2024112008450710000_8.2.e202403075.37","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw076"},{"key":"2024112008450710000_8.2.e202403075.38","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt400"},{"key":"2024112008450710000_8.2.e202403075.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2023.03.021"},{"key":"2024112008450710000_8.2.e202403075.40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021685"},{"key":"2024112008450710000_8.2.e202403075.41","doi-asserted-by":"publisher","DOI":"10.1038\/35065105"},{"key":"2024112008450710000_8.2.e202403075.42","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02018"},{"key":"2024112008450710000_8.2.e202403075.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2021.10.003"},{"key":"2024112008450710000_8.2.e202403075.44","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800724R"},{"key":"2024112008450710000_8.2.e202403075.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2021.03.017"},{"key":"2024112008450710000_8.2.e202403075.46","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11102830"},{"key":"2024112008450710000_8.2.e202403075.47","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0705-833"},{"key":"2024112008450710000_8.2.e202403075.48","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab382"},{"key":"2024112008450710000_8.2.e202403075.49","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2024112008450710000_8.2.e202403075.50","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks042"},{"key":"2024112008450710000_8.2.e202403075.51","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.90207.2008"},{"key":"2024112008450710000_8.2.e202403075.52","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12041"},{"key":"2024112008450710000_8.2.e202403075.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-023-00520-1"}],"container-title":["Life Science Alliance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.26508\/lsa.202403075","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T11:45:24Z","timestamp":1732103124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.life-science-alliance.org\/lookup\/doi\/10.26508\/lsa.202403075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":53,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,11,20]]},"published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.26508\/lsa.202403075"],"URL":"https:\/\/doi.org\/10.26508\/lsa.202403075","relation":{},"ISSN":["2575-1077"],"issn-type":[{"value":"2575-1077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}