PMID- 15672447 OWN - NLM STAT- MEDLINE DCOM- 20050715 LR - 20071115 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 79 IP - 6 DP - 2005 Mar 15 TI - Identification and characterization of Caenorhabditis elegans palmitoyl protein thioesterase1. PG - 836-48 AB - 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. CI - Copyright 2005 Wiley-Liss, Inc. FAU - Porter, Morwenna Y AU - Porter MY AD - Department of Paediatrics and Child Health, Royal Free and University College Medical School, University College London, London, United Kingdom. FAU - Turmaine, Mark AU - Turmaine M FAU - Mole, Sara E AU - Mole SE LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (RNA, Messenger) RN - EC 3.1.2.- (Thiolester Hydrolases) RN - EC 3.1.2.22 (palmitoyl-protein thioesterase) RN - EC 3.2.1.23 (beta-Galactosidase) RN - EC 3.2.1.52 (beta-N-Acetylhexosaminidases) SB - IM MH - Age Factors MH - Amino Acid Sequence MH - Animals MH - Animals, Genetically Modified/physiology MH - Blotting, Northern/methods MH - Caenorhabditis elegans/*enzymology/genetics/ultrastructure MH - Caenorhabditis elegans Proteins/chemistry/genetics/*metabolism MH - Cell Count MH - Cell Size MH - Computational Biology/methods MH - Humans MH - Microscopy, Electron, Transmission/methods MH - Mitochondria/pathology/ultrastructure MH - Mutation MH - Neurons/pathology/ultrastructure MH - Phenotype MH - RNA, Messenger/metabolism MH - Reproduction/genetics MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Sequence Alignment MH - Sequence Analysis, DNA/methods MH - Sequence Homology MH - Thiolester Hydrolases/chemistry/genetics/*metabolism MH - beta-Galactosidase/metabolism MH - beta-N-Acetylhexosaminidases/metabolism EDAT- 2005/01/27 09:00 MHDA- 2005/07/16 09:00 CRDT- 2005/01/27 09:00 PHST- 2005/01/27 09:00 [pubmed] PHST- 2005/07/16 09:00 [medline] PHST- 2005/01/27 09:00 [entrez] AID - 10.1002/jnr.20403 [doi] PST - ppublish SO - J Neurosci Res. 2005 Mar 15;79(6):836-48. doi: 10.1002/jnr.20403.