{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:52:10Z","timestamp":1789667530092,"version":"4.0.1"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":38,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01CA190688,R01CA236911,R01HL168659,R01HL158800,R01HL158875,K01OD026527"],"award-info":[{"award-number":["R01CA190688,R01CA236911,R01HL168659,R01HL158800,R01HL158875,K01OD026527"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,8]]},"abstract":"<jats:p>\n                    Rare diseases are underrepresented in biomedical research, leading to insufficient awareness. Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare disease caused by genetic alterations that result in heterozygous loss of function of SON. While patients with ZTTK syndrome live with numerous symptoms, the lack of model organisms hampers our understanding of SON and this complex syndrome. Here, we developed\n                    <jats:italic>Son<\/jats:italic>\n                    haploinsufficiency (\n                    <jats:italic>\n                      Son\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice as a model of ZTTK syndrome and identified the indispensable roles of\n                    <jats:italic>Son<\/jats:italic>\n                    in organ development and hematopoiesis.\n                    <jats:italic>\n                      Son\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice recapitulated clinical symptoms of ZTTK syndrome, including growth retardation, cognitive impairment, skeletal abnormalities, and kidney agenesis. Furthermore, we identified hematopoietic abnormalities in\n                    <jats:italic>\n                      Son\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice, including leukopenia and immunoglobulin deficiency, similar to those observed in human patients. Surface marker analyses and single-cell transcriptome profiling of hematopoietic stem and progenitor cells revealed that\n                    <jats:italic>Son<\/jats:italic>\n                    haploinsufficiency shifted cell fate more toward the myeloid lineage but compromised lymphoid lineage development by reducing genes required for lymphoid and B cell lineage specification. Additionally,\n                    <jats:italic>Son<\/jats:italic>\n                    haploinsufficiency caused inappropriate activation of erythroid genes and impaired erythropoiesis. These findings highlight the importance of the full gene expression of\n                    <jats:italic>Son<\/jats:italic>\n                    in multiple organs. Our model serves as an invaluable research tool for this rare disease and related disorders associated with SON dysfunction.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.175053","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T16:01:17Z","timestamp":1706630477000},"source":"Crossref","is-referenced-by-count":8,"title":["A mouse model of Zhu-Tokita-Takenouchi-Kim syndrome reveals indispensable SON functions in organ development and hematopoiesis"],"prefix":"10.1172","volume":"9","author":[{"given":"Lana","family":"Vukadin","sequence":"first","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohye","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huashi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Elkholy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2185-4948","authenticated-orcid":true,"given":"Alex","family":"Torrelli-Diljohn","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Metastasis Branch, Division of Cancer Biology, National Cancer Center, Goyang, Gyeonggi-do, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyuho","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, Dongguk University, Gyeongju, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin A.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Dunlap","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Gehrs","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Gyoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay Prakash","family":"Sah","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth N.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4044-2113","authenticated-orcid":true,"given":"Denise","family":"Stanford","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Barrington","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6621-6096","authenticated-orcid":true,"given":"Jeremy B.","family":"Foote","sequence":"additional","affiliation":[{"name":"Department of Microbiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna G.","family":"Sorace","sequence":"additional","affiliation":[{"name":"Department of Radiology and"},{"name":"O\u2019Neal Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Welner","sequence":"additional","affiliation":[{"name":"O\u2019Neal Comprehensive Cancer Center, and"},{"name":"Department of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Blake E.","family":"Hildreth","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"},{"name":"O\u2019Neal Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0323-8607","authenticated-orcid":true,"given":"Ssang-Taek Steve","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"},{"name":"O\u2019Neal Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Young Erin","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Molecular and Cellular Pathology, and"},{"name":"O\u2019Neal Comprehensive Cancer Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0049-9"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-019-00180-y"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101123"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-018-0049-4"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.039271"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.029"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.035"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.191"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37761"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.01.025"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00960-4"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.953"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23326"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/pde.14113"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1432"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200062"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.03.014"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-02-0126"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.092239"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24672"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2839"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.02.024"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60579"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.03.006"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abl4150"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101330200"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802696105"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1969.tb12982.x"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8994-2_9"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/0166-4328(94)90008-6"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8994-2_10"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3791\/55718"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.05.003"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.06.004"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.07.005"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.595"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.132.1.332"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.1.75"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg522"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.01.010"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2008.07.004"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1836009"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.1.377"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.3.1049"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1101\/gad.959102"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205326"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.133.4.1710"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2007.07.006"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-178"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02894"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503280102"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000834107"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111490"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2016.11.002"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100351"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112304"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27562-4"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/175053\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:41:05Z","timestamp":1779140465000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/175053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,30]]},"references-count":57,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,1,23]]},"published-print":{"date-parts":[[2024,3,8]]}},"alternative-id":["10.1172\/jci.insight.175053"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.175053","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,30]]},"article-number":"e175053"}}