{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:19:58Z","timestamp":1787062798836,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1RM1 NS132962"],"award-info":[{"award-number":["1RM1 NS132962"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R38 AI74266"],"award-info":[{"award-number":["1R38 AI74266"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007268","name":"Washington University in St. Louis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Krabbe Disease (KD) is a lysosomal leukodystrophy characterized by the production of psychosine in oligodendrocytes, leading to neurodegeneration and ultimately death. The only treatment modality currently available for this disease is hematopoietic stem cell transplantation (HSCT), a procedure with high morbidity, highlighting the need for further therapies to be developed. In this study, we established and characterized\n                    <jats:italic>GALC<\/jats:italic>\n                    knockout MO3.13 cells, a cell line derived from human oligodendrocytes, as a model for KD. Clonal MO3.13 cells with\n                    <jats:italic>GALC<\/jats:italic>\n                    KO were obtained via CRISPR\/Cas9\u2010mediated gene editing. GALC activity was measured by a 4\u2010methylumbellyferyl (4\u2010MU)\u2010based assay, and morphology analyses were performed using light microscopy and transmission electron microscopy. Psychosine was measured by liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS). The\n                    <jats:italic>GALC<\/jats:italic>\n                    KO cells have elevated levels of psychosine and an increased number of autophagosomes, autolysosomes, and cytoplasmic granules on transmission electron microscopy. Glycogen abundance was decreased in\n                    <jats:italic>GALC<\/jats:italic>\n                    KO cells compared to controls. After administration of BMN\u2010S202, a ceramide galactosyltransferase inhibitor, psychosine levels in\n                    <jats:italic>GALC<\/jats:italic>\n                    KO cells were reduced back to WT levels. In conclusion, we demonstrated that the\n                    <jats:italic>GALC<\/jats:italic>\n                    KO MO3.13 cell line recapitulates the KD phenotype and biochemical response to SRT and may be a useful KD model for mechanistic studies and therapeutic development for KD.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70212","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T03:56:08Z","timestamp":1781150168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Validating a Human Cell Model of Null Galactosylceramidase (\n                    <scp>GALC<\/scp>\n                    ) Enzyme Activity That Recapitulates Krabbe Disease"],"prefix":"10.1002","volume":"49","author":[{"given":"Rodrigo T.","family":"Starosta","sequence":"first","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Molecular and Medical Genetics Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazia","family":"Khatoon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie S.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Medicine Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Q.","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Austin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Cui","sequence":"additional","affiliation":[{"name":"McDonnell Genomics Institute, Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Strout","sequence":"additional","affiliation":[{"name":"Washington University Center for Cellular Imaging  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuntian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medicine Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Sands","sequence":"additional","affiliation":[{"name":"Department of Medicine Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia I.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201002361\u2010y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.40.25880"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490010106"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20406"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1912108116"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24008"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20102008\u20101052380"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006\u2010291x(87)80472\u20102"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/103.3.695"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.09.017"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2001.3194"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt190"},{"issue":"2","key":"e_1_2_10_14_1","first-page":"165","article-title":"Globoid Cell Leukodystrophy (Krabbe Type) in the Dog","volume":"149","author":"Fletcher T. F.","year":"1966","journal-title":"Journal of the American Veterinary Medical Association"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2019.103451"},{"issue":"5","key":"e_1_2_10_16_1","first-page":"476","article-title":"Genetic Galactocerebrosidase Deficiency (Globoid Cell Leukodystrophy, Krabbe Disease) in Rhesus Monkeys (\n                     Macaca mulatta\n                  )","volume":"48","author":"Baskin G. B.","year":"1998","journal-title":"Laboratory Animal Science"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1357\u20104310(00)01800\u20101"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010018\u20100766\u2010x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.06.020"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005477"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.52114"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2025.101669"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480260212"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1027324230923"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.4235"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01677415"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.07.002"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201093601\u20101"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.09.046"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.2003.01941.x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600084\u2010JLR200"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2008.05279.x"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23910"},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","unstructured":"R. T.Starosta S. Q.Le X.Cui et\u00a0al. \u201cDecrease in Psychosine in Response to a Ceramide Galactosyltransferase Inhibitor in a Novel Human Cell Model of Krabbe Disease. Presented at: WORLD Symposium; 2024; San Diego CA\u201d.","DOI":"10.1016\/j.ymgme.2023.108048"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.110315"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.05.011"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116351"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70212","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.70212","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70212","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:19:09Z","timestamp":1785298749000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/jimd.70212"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70212","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]},"assertion":[{"value":"2026-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70212"}}