Porter_2005_J.Neurosci.Res_79_836

Infantile neuronal ceroid lipofuscinosis (INCL; Batten disease) is a severe neurodegenerative disorder of childhood characterized by the accumulation of autofluorescent storage material in lysosomes. It is caused by mutation of the CLN1/PPT1 gene, which encodes the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1), but the mechanism of disease pathogenesis and substrates for the enzyme are unknown. Caenorhabditis elegans is a simple nematode worm, with a fully sequenced genome, which is easy to maintain and manipulate. It has a completely mapped cell lineage and nervous system and has already provided clues about the pathogenesis of several human neuronal and lysosomal storage disorders. We have identified and characterized a PPT1 homologue in C. elegans. We found that, although this gene was not essential for the animal's survival, its mutation resulted in a mild developmental and reproductive phenotype, affected the number and size of mitochondria, and resulted in an abnormality in mitochondrial morphology, possibly suggestive of a role for this organelle in INCL pathogenesis. This strain, deleted for ppt-1, potentially provides a model system for the study of PPT1 and the pathogenesis of INCL.