{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:13:44Z","timestamp":1787807624756,"version":"build-2784847793"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T00:00:00Z","timestamp":1519257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000304","name":"Parkinson's UK","doi-asserted-by":"publisher","award":["H-1501"],"award-info":[{"award-number":["H-1501"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS073813"],"award-info":[{"award-number":["R01NS073813"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation for JNCL Research"},{"name":"NCL-Stiftung"},{"name":"Stichting BeatBatten!"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model (Cln3\u0394ex7\/8 mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3\u0394ex7\/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of \u03b2-1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase), which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3\u0394ex7\/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis.<\/jats:p>","DOI":"10.3390\/ijms19020625","type":"journal-article","created":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T12:04:42Z","timestamp":1519301082000},"page":"625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis"],"prefix":"10.3390","volume":"19","author":[{"given":"Aleksandra","family":"Somogyi","sequence":"first","affiliation":[{"name":"Center for Membrane Proteomics, Goethe University of Frankfurt, 60438 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3143-3867","authenticated-orcid":false,"given":"Anton","family":"Petcherski","sequence":"additional","affiliation":[{"name":"Center for Membrane Proteomics, Goethe University of Frankfurt, 60438 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Beckert","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35292 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mylene","family":"Huebecker","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Priestman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Banning","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35292 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Cotman","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital Research Institute, Harvard Medical School, 185 Cambridge Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika O.","family":"Ruonala","sequence":"additional","affiliation":[{"name":"Center for Membrane Proteomics, Goethe University of Frankfurt, 60438 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8393-1825","authenticated-orcid":false,"given":"Ritva","family":"Tikkanen","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35292 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1093\/hmg\/11.22.2709","article-title":"Cln3(Deltaex7\/8) knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth","volume":"11","author":"Cotman","year":"2002","journal-title":"Hum. 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