{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:02:47Z","timestamp":1791288167756,"version":"4.3.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["GNT1136567"],"award-info":[{"award-number":["GNT1136567"]}]},{"name":"National Health and Medical Research Council of Australia","award":["GNT1144159"],"award-info":[{"award-number":["GNT1144159"]}]},{"name":"National Health and Medical Research Council of Australia","award":["1025008"],"award-info":[{"award-number":["1025008"]}]},{"name":"National Health and Medical Research Council of Australia","award":["573732"],"award-info":[{"award-number":["573732"]}]},{"name":"National Health and Medical Research Council of Australia","award":["GNT2016338"],"award-info":[{"award-number":["GNT2016338"]}]},{"name":"NSW Health Cardiovascular Research Capacity Program","award":["GNT1136567"],"award-info":[{"award-number":["GNT1136567"]}]},{"name":"NSW Health Cardiovascular Research Capacity Program","award":["GNT1144159"],"award-info":[{"award-number":["GNT1144159"]}]},{"name":"NSW Health Cardiovascular Research Capacity Program","award":["1025008"],"award-info":[{"award-number":["1025008"]}]},{"name":"NSW Health Cardiovascular Research Capacity Program","award":["573732"],"award-info":[{"award-number":["573732"]}]},{"name":"NSW Health Cardiovascular Research Capacity Program","award":["GNT2016338"],"award-info":[{"award-number":["GNT2016338"]}]},{"name":"Estate of the Late RT Hall and the St Vincent\u2019s Clinic Foundation","award":["GNT1136567"],"award-info":[{"award-number":["GNT1136567"]}]},{"name":"Estate of the Late RT Hall and the St Vincent\u2019s Clinic Foundation","award":["GNT1144159"],"award-info":[{"award-number":["GNT1144159"]}]},{"name":"Estate of the Late RT Hall and the St Vincent\u2019s Clinic Foundation","award":["1025008"],"award-info":[{"award-number":["1025008"]}]},{"name":"Estate of the Late RT Hall and the St Vincent\u2019s Clinic Foundation","award":["573732"],"award-info":[{"award-number":["573732"]}]},{"name":"Estate of the Late RT Hall and the St Vincent\u2019s Clinic Foundation","award":["GNT2016338"],"award-info":[{"award-number":["GNT2016338"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Dilated cardiomyopathy (DCM) is a common heart muscle disorder that frequently leads to heart failure, arrhythmias, and death. While DCM is often heritable, disease-causing mutations are identified in only ~30% of cases. In a forward genetic mutagenesis screen, we identified a novel zebrafish mutant, heart and head (hahvcc43), characterized by early-onset cardiomyopathy and craniofacial defects. Linkage analysis and next-generation sequencing identified a nonsense variant in the highly conserved scfd1 gene, also known as sly1, that encodes sec1 family domain-containing 1. Sec1\/Munc18 proteins, such as Scfd1, are involved in membrane fusion regulating endoplasmic reticulum (ER)\/Golgi transport. CRISPR\/Cas9-engineered scfd1vcc44 null mutants showed severe cardiac and craniofacial defects and embryonic lethality that recapitulated the phenotype of hahvcc43 mutants. Electron micrographs of scfd1-depleted cardiomyocytes showed reduced myofibril width and sarcomere density, as well as reticular network disorganization and fragmentation of Golgi stacks. Furthermore, quantitative PCR analysis showed upregulation of ER stress response and apoptosis markers. Both heterozygous hahvcc43 mutants and scfd1vcc44 mutants survived to adulthood, showing chamber dilation and reduced ventricular contraction. Collectively, our data implicate scfd1 loss-of-function as the genetic defect at the hahvcc43 locus and provide new insights into the role of scfd1 in cardiac development and function.<\/jats:p>","DOI":"10.3390\/jcdd10100408","type":"journal-article","created":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:46:21Z","timestamp":1695552381000},"page":"408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Loss of Sec-1 Family Domain-Containing 1 (scfd1) Causes Severe Cardiac Defects and Endoplasmic Reticulum Stress in Zebrafish"],"prefix":"10.3390","volume":"10","author":[{"given":"Inken G.","family":"Huttner","sequence":"first","affiliation":[{"name":"Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia"},{"name":"School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine F.","family":"Santiago","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia"},{"name":"School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8575-0534","authenticated-orcid":false,"given":"Delfine","family":"Cheng","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, 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3800, Australia"},{"name":"European Molecular Biology Labs (EMBL) Australia, Victorian Node, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-9760","authenticated-orcid":false,"given":"Kelly A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Physiology, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-9856","authenticated-orcid":false,"given":"Diane","family":"Fatkin","sequence":"additional","affiliation":[{"name":"Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia"},{"name":"School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW 2052, Australia"},{"name":"Cardiology Department, St Vincent\u2019s Hospital, Darlinghurst, NSW 2010, 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