{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:16:34Z","timestamp":1782123394818,"version":"3.54.5"},"reference-count":31,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T00:00:00Z","timestamp":1552262400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M004597\/1"],"award-info":[{"award-number":["MR\/M004597\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L009978\/1"],"award-info":[{"award-number":["MR\/L009978\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000317","name":"Action Medical Research","doi-asserted-by":"publisher","award":["GN2595"],"award-info":[{"award-number":["GN2595"]}],"id":[{"id":"10.13039\/501100000317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Lenz-Majewski\u00a0syndrome (LMS)\u00a0is characterized by osteosclerosis and hyperostosis of skull, vertebrae and tubular bones as well as craniofacial, dental, cutaneous, and digit abnormalities. We previously found that LMS is caused by\n                    <ns4:italic>de novo<\/ns4:italic>\n                    dominant missense mutations in the\u00a0\n                    <ns4:italic>PTDSS1<\/ns4:italic>\n                    \u00a0gene, which encodes phosphatidylserine synthase 1 (PSS1), an enzyme that catalyses the conversion of phosphatidylcholine to phosphatidylserine. The mutations causing LMS result in a gain-of-function, leading to increased enzyme activity and blocking end-product inhibition of PSS1.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    Here, we have used transpose-mediated transgenesis to attempt to stably express wild-type and mutant forms of human\n                    <ns4:italic>PTDSS1<\/ns4:italic>\n                    ubiquitously or specifically in chondrocytes, osteoblasts or osteoclasts in zebrafish.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    We report multiple genomic integration sites for each of 8 different transgenes. While we confirmed that the ubiquitously driven transgene constructs were functional in terms of driving gene expression following transient transfection in HeLa cells, and that all lines exhibited expression of a heart-specific cistron within the transgene, we failed to detect\n                    <ns4:italic>PTDSS1<\/ns4:italic>\n                    gene expression at either the RNA or protein levels in zebrafish. All wild-type and mutant transgenic lines of zebrafish exhibited mild scoliosis with variable incomplete penetrance which was never observed in non-transgenic animals.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    Collectively the data suggest that the transgenes are silenced, that animals with integrations that escape silencing are not viable, or that other technical factors prevent transgene expression. In conclusion, the incomplete penetrance of the phenotype and the lack of a matched transgenic control model precludes further meaningful investigations of these transgenic lines.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.17314.1","type":"journal-article","created":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T10:40:06Z","timestamp":1552300806000},"page":"273","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Analysis of transgenic zebrafish expressing the Lenz-Majewski syndrome gene PTDSS1 in skeletal cell lineages"],"prefix":"10.12688","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-3585","authenticated-orcid":false,"given":"Marian","family":"Seda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Peskett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalambos","family":"Demetriou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun E.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9340-8117","authenticated-orcid":false,"given":"Philip","family":"Stanier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3293-2999","authenticated-orcid":false,"given":"Dagan","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2019,3,11]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"12888-12897","DOI":"10.1074\/jbc.M800714200","article-title":"Defining the importance of phosphatidylserine synthase-1 (PSS1): unexpected viability of PSS1-deficient mice.","volume":"283","author":"D Arikketh","year":"2008","journal-title":"J Biol Chem."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"183-196","DOI":"10.1016\/j.tig.2017.01.001","article-title":"Understanding Idiopathic Scoliosis: A New Zebrafish School of Thought.","volume":"33","author":"C Boswell","year":"2017","journal-title":"Trends Genet."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"96-109","DOI":"10.1016\/j.ydbio.2011.09.013","article-title":"Osteoclasts in bone modeling, as revealed by in vivo imaging, are essential for organogenesis in fish.","volume":"360","author":"M Chatani","year":"2011","journal-title":"Dev Biol."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"470-474","DOI":"10.1002\/ajmg.1320320407","article-title":"Skeletal dysplasia syndrome with progeroid appearance, characteristic facial and limb anomalies, multiple synostoses, and distinct skeletal changes: a variant example of the Lenz-Majewski syndrome.","volume":"32","author":"K Chrzanowska","year":"1989","journal-title":"Am J Med Genet."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"686-689","DOI":"10.1007\/s10038-007-0165-y","article-title":"A Japanese patient with a mild Lenz-Majewski syndrome.","volume":"52","author":"S Dateki","year":"2007","journal-title":"J Hum Genet."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"518-31","DOI":"10.1016\/j.ydbio.2011.06.020","article-title":"Identification of an evolutionarily conserved regulatory element of the zebrafish col2a1a gene.","volume":"357","author":"R Dale","year":"2011","journal-title":"Dev Biol."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/1471-2148-12-27","article-title":"Evolution of the osteoblast: skeletogenesis in gar and zebrafish.","volume":"12","author":"B Eames","year":"2012","journal-title":"BMC Evol Biol."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"784-96","DOI":"10.1038\/nrd916","article-title":"Discoveries, drugs and skeletal disorders.","volume":"1","author":"D Goltzman","year":"2002","journal-title":"Nat Rev Drug Discov."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"129-131","DOI":"10.1148\/radiology.149.1.6611917","article-title":"Lenz-Majewski syndrome.","volume":"149","author":"R Gorlin","year":"1983","journal-title":"Radiology."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"3088-3099","DOI":"10.1002\/dvdy.21343","article-title":"The Tol2kit: a multisite gateway-based construction kit for Tol2 transposon transgenesis constructs.","volume":"236","author":"K Kwan","year":"2007","journal-title":"Dev Dyn."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/bonekey.2013.179","article-title":"A bone to pick with zebrafish.","volume":"2","author":"E Mackay","year":"2013","journal-title":"Bonekey Rep."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"335-338","DOI":"10.1002\/1096-8628(20000814)93:4%3c335::AID-AJMG14%3e3.0.CO;2-5","article-title":"Lenz-Majewski hyperostotic dwarfism: reexamination of the original patient.","volume":"93","author":"F Majewski","year":"2000","journal-title":"Am J Med Genet."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"1567-1570","DOI":"10.1007\/s00247-015-3329-5","article-title":"Craniovertebral junction stenosis in Lenz-Majewski syndrome.","volume":"45","author":"K Mizuguchi","year":"2015","journal-title":"Pediatr Radiol."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"235-269","DOI":"10.1016\/bs.ctdb.2015.07.001","article-title":"Zebrafish Craniofacial Development: A Window into Early Patterning.","volume":"115","author":"L Mork","year":"2015","journal-title":"Curr Top Dev Biol."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"87-92","DOI":"10.1002\/(SICI)1096-8628(19970711)71:1<87::AID-AJMG16>3.0.CO;2-R","article-title":"Craniotubular dysplasia with severe postnatal growth retardation, mental retardation, ectodermal dysplasia, and loose skin: Lenz-Majewski-like syndrome.","volume":"71","author":"G Nishimura","year":"1997","journal-title":"Am J Med Genet."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"668-675","DOI":"10.1002\/ajmg.a.38604","article-title":"Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1.","volume":"176","author":"J Piard","year":"2018","journal-title":"Am J Med Genet A."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"198-200","DOI":"10.1002\/(SICI)1096-8628(20000320)91:3>198::AID-AJMG8<3.0.CO;2-4","article-title":"Dysgenesis of corpus callosum in Lenz-Majewski hyperostotic dwarfism.","volume":"91","author":"J Saraiva","year":"2000","journal-title":"Am J Med Genet."},{"key":"ref-18","doi-asserted-by":"crossref","first-page":"2945-2960","DOI":"10.1242\/dev.124.15.2945","article-title":"Musculoskeletal patterning in the pharyngeal segments of the zebrafish embryo.","volume":"124","author":"T Schilling","year":"1997","journal-title":"Development."},{"key":"ref-19","article-title":"Analysis of transgenic zebrafish expressing the Lenz-Majewski syndrome gene PTDSS1 in skeletal cell lineages..","author":"M Seda","year":"2019","journal-title":"figshare."},{"key":"ref-20","first-page":"211-224","article-title":"Osteoclast-like Cells in Early Zebrafish Embryos.","volume":"16","author":"F Sharif","year":"2014","journal-title":"Cell J."},{"key":"ref-21","first-page":"45-52","article-title":"Lenz-Majewski syndrome associated with hydrocephalus and multiple congenital malformations.","volume":"4","author":"M Shoja","year":"2013","journal-title":"Biomd Int."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"70-76","DOI":"10.1038\/ng.2829","article-title":"Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome.","volume":"46","author":"S Sousa","year":"2014","journal-title":"Nat Genet."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"57-64","DOI":"10.1042\/bj3420057","article-title":"Cloning and expression of murine liver phosphatidylserine synthase (PSS)-2: differential regulation of phospholipid metabolism by PSS1 and PSS2.","volume":"342","author":"S Stone","year":"1999","journal-title":"Biochem. J."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"392-399","DOI":"10.1016\/j.ejmg.2015.06.002","article-title":"Lenz-Majewski syndrome: Report of a case with novel mutation in PTDSS1 gene.","volume":"58","author":"P Tamhankar","year":"2015","journal-title":"Eur J Med Genet."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"141-50","DOI":"10.1242\/dev.071035","article-title":"Rankl-induced osteoclastogenesis leads to loss of mineralization in a medaka osteoporosis model.","volume":"139","author":"T To","year":"2012","journal-title":"Development."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"923-944","DOI":"10.1194\/jlr.R084004","article-title":"Historical perspective: phosphatidylserine and phosphatidylethanolamine from the 1800s to the present.","volume":"59","author":"J Vance","year":"2018","journal-title":"J Lipid Res."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"543-554","DOI":"10.1016\/j.bbalip.2012.08.016","article-title":"Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells.","volume":"1831","author":"J Vance","year":"2013","journal-title":"Biochim Biophys Acta."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"137-142","DOI":"10.1097\/01.mcd.0000127468.11641.b7","article-title":"Expanding the phenotypic spectrum of Lenz-Majewski syndrome: facial palsy, cleft palate and hydrocephalus.","volume":"13","author":"D Wattanasirichaigoon","year":"2004","journal-title":"Clin Dysmorphol."},{"key":"ref-29","article-title":"The zebrafish book","author":"M Westerfield","year":"1993"},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"606-614","DOI":"10.1002\/jbmr.2398","article-title":"Lenz-Majewski hyperostotic dwarfism with hyperphosphoserinuria from a novel mutation in PTDSS1 encoding phosphatidylserine synthase 1.","volume":"30","author":"M Whyte","year":"2015","journal-title":"J Bone Miner Res."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"3827-3838","DOI":"10.1074\/jbc.M707653200","article-title":"Analysis and molecular modeling of the formation, structure, and activity of the phosphatidylserine-calcium-phosphate complex associated with biomineralization.","volume":"283","author":"L Wu","year":"2008","journal-title":"J Biol Chem."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/8-273\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-273\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/8-273\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T13:10:03Z","timestamp":1663074603000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/8-273\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,11]]},"references-count":31,"URL":"https:\/\/doi.org\/10.12688\/f1000research.17314.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.18933.r45567","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.18933.r48264","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.18933.r48264","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.18933.r45567","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,11]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/8-273\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.18933.r45567, Jean-Marie Delalande, Blizard Institute, Barts and The London School of Medicine and Dentistry, Centre for Immunology, Queen Mary University of London, London, UK, 25 Mar 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-273\/v1#referee-response-45567","order":0,"name":"referee-response-45567","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.18933.r48264, Carles Gaston-Massuet, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK, 03 Jun 2019, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/8-273\/v1#referee-response-48264","order":1,"name":"referee-response-48264","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was funded by a Medical Research Council Project Grant (MR\/M004597\/1) to PS, and a Medical Research Council New Investigator Research Grant (MR\/L009978\/1) and Action Medical Research Project Grant (GN2595) to DJ. PS is supported by Great Ormond Street Hospital Children\u2019s Charity and the research was also supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}