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Alliance"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:p>\n                    Juvenile neuronal ceroid lipofuscinosis (or Batten disease) is an autosomal recessive, rare neurodegenerative disorder that affects mainly children above the age of 5 yr and is most commonly caused by mutations in the highly conserved\n                    <jats:italic>CLN3<\/jats:italic>\n                    gene. Here, we generated\n                    <jats:italic>cln3<\/jats:italic>\n                    morphants and stable mutant lines in zebrafish. Although neither morphant nor mutant\n                    <jats:italic>cln3<\/jats:italic>\n                    larvae showed any obvious developmental or morphological defects, behavioral phenotyping of the mutant larvae revealed hyposensitivity to abrupt light changes and hypersensitivity to pro-convulsive drugs. Importantly, in-depth metabolomics and lipidomics analyses revealed significant accumulation of several glycerophosphodiesters (GPDs) and cholesteryl esters, and a global decrease in bis(monoacylglycero)phosphate species, two of which (GPDs and bis(monoacylglycero)phosphates) were previously proposed as potential biomarkers for\n                    <jats:italic>CLN3<\/jats:italic>\n                    disease based on independent studies in other organisms. We could also demonstrate GPD accumulation in human-induced pluripotent stem cell\u2013derived cerebral organoids carrying a pathogenic variant for\n                    <jats:italic>CLN3<\/jats:italic>\n                    . Our models revealed that GPDs accumulate at very early stages of life in the absence of functional CLN3 and highlight glycerophosphoinositol and BMP as promising biomarker candidates for pre-symptomatic\n                    <jats:italic>CLN3<\/jats:italic>\n                    disease.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202302057","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T01:07:33Z","timestamp":1704848853000},"page":"e202302057","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["CLN3 deficiency leads to neurological and metabolic perturbations during early development"],"prefix":"10.26508","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3517-5399","authenticated-orcid":true,"given":"Ursula","family":"Heins-Marroquin","sequence":"first","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-3400","authenticated-orcid":true,"given":"Randolph R","family":"Singh","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg"},{"id":[{"id":"https:\/\/ror.org\/00hj8s172","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University","place":[", New York, NY, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4779-7259","authenticated-orcid":true,"given":"Simon","family":"Perathoner","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, Bad Nauheim, 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sant\u00e9 (LNS), Dudelange, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc O","family":"Warmoes","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Mittelbronn","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg"},{"name":"National Center of Pathology (NCP), Laboratoire national de sant\u00e9 (LNS), Dudelange, Luxembourg"},{"name":"Department of Oncology (DONC), Luxembourg Institute of Health (LIH), Strassen, Luxembourg"},{"name":"Luxembourg Center of Neuropathology 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