Identification and characterization of Caenorhabditis elegans palmitoyl protein thioesterase1

✍ Scribed by Morwenna Y. Porter; Mark Turmaine; Sara E. Mole

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 833 KB
• Volume: 79
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20403

✦ Synopsis

Abstract

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. © 2005 Wiley‐Liss, Inc.