{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:00:02Z","timestamp":1772802002864,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The <jats:italic>CLN3<\/jats:italic> gene is involved in juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten\u2013Spielmeyer\u2013Vogt disease, a severe hereditary neurodegenerative lysosomal storage disorder characterized by progressive disease pathology, with loss of vision as the first symptom. Another characteristic of JNCL is the lysosomal accumulation of autofluorescent lipopigments, forming fingerprint storage patterns visible by electron microscopy. The function of the CLN3 protein is still unknown, although the evolutionarily conserved CLN3 protein is being functionally analysed using different experimental models. We have explored the potential of the nematode <jats:italic>Caenorhabditis elegans<\/jats:italic> as a model for Batten disease in order to bridge the gap between the unicellular yeast and very complex mouse JNCL models. <jats:italic>C. elegans<\/jats:italic> has three genes homologous to <jats:italic>CLN3<\/jats:italic>, for each of which deletion mutants were isolated. <jats:italic>Cln\u20103.1<\/jats:italic> deletion mutants have a decreased lifespan, and <jats:italic>cln\u20103.2<\/jats:italic> deletion mutants a decreased brood size. However, the neuronal or movement defects and aberrant lipopigment distribution or accumulation observed in JNCL were not found in the worms. To detect possible redundancy, single deletion mutants were crossed to obtain double and triple mutants, which were viable but showed no JNCL\u2010specific defects. The <jats:italic>cln\u20103<\/jats:italic> triple mutants show a more prominent decrease in lifespan and brood size, the latter most conspicuously at the end of the egg\u2010laying period, suggesting premature ageing. To focus our functional analysis we examined the <jats:italic>C. elegans cln\u20103<\/jats:italic> expression patterns, using promoter\u2013GFP (green fluorescent protein) gene fusions. Fluorescence patterns suggest <jats:italic>cln\u20103.1<\/jats:italic> expression in the intestine, <jats:italic>cln\u20103.2<\/jats:italic> expression in the hypoderm, and <jats:italic>cln\u20103.3<\/jats:italic> expression in intestinal muscle, male\u2010specific posterior muscle and hypoderm. Further life stage\u2010 and tissue\u2010specific analysis of the processes causing the phenotype of the <jats:italic>cln\u20103<\/jats:italic> triple mutants may provide more information about the function of the <jats:italic>cln\u20103<\/jats:italic> protein and contribute to a better understanding of the basic processes affected in Batten disease patients.<\/jats:p>","DOI":"10.1007\/s10545-005-0125-7","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T09:35:29Z","timestamp":1138181729000},"page":"1065-1080","source":"Crossref","is-referenced-by-count":14,"title":["Deletion of the <i>Caenorhabditis elegans<\/i> homologues of the <i>CLN3<\/i> gene, involved in human juvenile neuronal ceroid lipofuscinosis, causes a mild progeric phenotype"],"prefix":"10.1002","volume":"28","author":[{"given":"G.","family":"de Voer","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Center for Human and Clinical Genetics, Sylvius Laboratories Leiden University Medical Center PO Box 9503 Leiden RA 2300 The Netherlands"}]},{"given":"P.","family":"van der Bent","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Center for Human and Clinical Genetics, Sylvius Laboratories Leiden University Medical Center PO Box 9503 Leiden RA 2300 The Netherlands"}]},{"given":"A. J. G.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"ICVS, School of Health Sciences Minho University Gualtar Campus Braga Portugal"}]},{"given":"G.\u2010J. B.","family":"van Ommen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Center for Human and Clinical Genetics, Sylvius Laboratories Leiden University Medical Center PO Box 9503 Leiden RA 2300 The Netherlands"}]},{"given":"D. J. M.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Center for Human and Clinical Genetics, Sylvius Laboratories Leiden University Medical Center PO Box 9503 Leiden RA 2300 The Netherlands"}]},{"given":"P. E. M.","family":"Taschner","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Center for Human and Clinical Genetics, Sylvius Laboratories Leiden University Medical Center PO Box 9503 Leiden RA 2300 The Netherlands"}]}],"member":"311","published-online":{"date-parts":[[2005,12]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01279"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00831"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.4.606-612.2002"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.22.6418-6423.2000"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.6.869"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/ejpn.2000.0446"},{"key":"e_1_2_1_8_1","volume-title":"Methods in Cell Biology 48","author":"Epstein 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