Caenorhabditis elegans homologues of the CLN3 gene,mutated in juvenile neuronal ceroid lipofuscinosis

Voer, Gert de; Jansen, Gert; Ommen, Gert‐Jan B. van; Peters, Dorien J.M.; Taschner, Peter E.M.

doi:10.1053/ejpn.2000.0446

Cited by 4 publications

(1 citation statement)

References 17 publications

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“…Moreover, the nematode is a convenient model to explore human neurodegenerative diseases, as demonstrated by the development of disease models for Niemann-Pick type C (McKusick 257220), mucolipidosis type IV (McKusick 252650), and neurodegeneration caused by expanded polyglutamine repeats (Faber et al 2002;Fares and Greenwald 2001;Sym et al 2000). Since the C. elegans genome contains three CLN3 homologues (de Voer et al 2001), we report here the expression patterns of the three cln-3 genes and the phenotypes of C. elegans cln-3 mutants.…”

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confidence: 97%

Deletion of the Caenorhabditis elegans homologues of the CLN3 gene, involved in human juvenile neuronal ceroid lipofuscinosis, causes a mild progeric phenotype

Voer

Bent

Rodrigues

et al. 2005

J of Inher Metab Disea

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The CLN3 gene is involved in juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten-Spielmeyer-Vogt 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 Caenorhabditis elegans as a model for Batten disease in order to bridge the gap between the unicellular yeast and very complex mouse JNCL models. C. elegans has three genes homologous to CLN3, for each of which deletion mutants were isolated. Cln-3.1 deletion mutants have a decreased lifespan, and cln-3.2 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-specific defects. The cln-3 triple mutants show a more prominent decrease in lifespan and brood size, the latter most conspicuously at the end of the egg-laying period, suggesting premature ageing. To focus our functional analysis we examined the C. elegans cln-3 expression patterns, using promoter-GFP (green fluorescent protein) gene fusions. Fluorescence patterns suggest cln-3.1 expression in the intestine, cln-3.2 expression in the hypoderm, and cln-3.3 expression in intestinal muscle, male-specific posterior muscle and hypoderm. Further life stage- and tissue-specific analysis of the processes causing the phenotype of the cln-3 triple mutants may provide more information about the function of the cln-3 protein and contribute to a better understanding of the basic processes affected in Batten disease patients.

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mentioning

confidence: 97%

Deletion of the Caenorhabditis elegans homologues of the CLN3 gene, involved in human juvenile neuronal ceroid lipofuscinosis, causes a mild progeric phenotype

Voer

Bent

Rodrigues

et al. 2005

J of Inher Metab Disea

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Neuronal Ceroid-Lipofuscinoses

Tyynelä

Lysosomes

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Characterizing pathogenic processes in Batten disease: Use of small eukaryotic model systems

Phillips

Muzaffar

Codlin

et al. 2006

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The neuronal ceroid lipofuscinoses (NCLs) are neurodegenerative disorders. Nevertheless, small model organisms, including those lacking a nervous system, have proven invaluable in the study of mechanisms that underlie the disease and in studying the functions of the conserved proteins associated to each disease. From the single-celled yeast, Saccharomyces cerevisiae and Schizosaccharomyces pombe, to the worm, Caenorhabditis elegans and the fruitfly, Drosophila melanogaster, biochemical and, in particular, genetic studies on these organisms have provided insight into the NCLs.

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Caenorhabditis elegans homologues of the CLN3 gene,mutated in juvenile neuronal ceroid lipofuscinosis

Cited by 4 publications

References 17 publications

Deletion of the Caenorhabditis elegans homologues of the CLN3 gene, involved in human juvenile neuronal ceroid lipofuscinosis, causes a mild progeric phenotype

Deletion of the Caenorhabditis elegans homologues of the CLN3 gene, involved in human juvenile neuronal ceroid lipofuscinosis, causes a mild progeric phenotype

Neuronal Ceroid-Lipofuscinoses

Characterizing pathogenic processes in Batten disease: Use of small eukaryotic model systems

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