The cln-3 genes of Caenorhabditis elegans : making C. elegans models for Juvenile Neuronal Ceroid Lipofuscinosis.

Voer, G. de (2008)

Doctoral Thesis

The most common neurodegenerative genetic childhood disease, juvenile neuronal ceroid lipofuscinosis (JNCL), is a lysosomal storage disorder that is caused by mutations in the CLN3 gene. In patients' lysosomes material accumulates primarily composed of Subunit c. How mutations in CLN3 lead to this disease is unknown. The nematode Caenorhabditis elegans is useful for researching genetic neurodegenerative diseases. C. elegans has three CLN3 homologous proteins, cln-3.1, cln-3.2, and cln-3.3. Nematode cln-3 mutants were generated, crossed to obtain double and triple mutants, and their phenotypes were studied. Cln-3 triple mutants have slightly decreased life span and little decreased brood size. This triple mutant is viable, indicating that cln-3 genes are not essential for nematode life under laboratory conditions. These phenotypes are not useable in genetic screens and no neurological or other robust phenotypes were present. Expression analysis was performed to focus the phenotypic analysis. The short life span of C. elegans may explain the lack of accumulated materials. Therefore, Subunit c was inducibly overexpressed in cln-3 triple mutants. This is deleterious to nematodes, appearing to affect mitochondrial ultrastructure, although similar in wildtype and cln-3 mutants. Additional experiments with this nematode model may increase our understanding of the function of the cln-3 genes.

• Batten disease
• Caenorhabditis elegans
• CLN3
• JNCL
• Lysosome
• Neuronal Ceroid Lipofuscinosis

• All authors: Voer, G. de
• Supervisor: Ommen, G.J.B. van
• Co-supervisor: Taschner, P.E.M.; Peters, D.J.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2008-05-07
• ISBN (print): 9789090226422
• Sponsorship: Jurriaanse Stichting, Genzyme Europe BV