PMID- 16452138
OWN - NLM
STAT- MEDLINE
DCOM- 20060717
LR  - 20231105
IS  - 0016-6731 (Print)
IS  - 0016-6731 (Linking)
VI  - 172
IP  - 4
DP  - 2006 Apr
TI  - Palmitoyl-protein thioesterase 1 deficiency in Drosophila melanogaster causes 
      accumulation of abnormal storage material and reduced life span.
PG  - 2379-90
AB  - Human neuronal ceroid lipofuscinoses (NCLs) are a group of genetic 
      neurodegenerative diseases characterized by progressive death of neurons in the 
      central nervous system (CNS) and accumulation of abnormal lysosomal storage 
      material. Infantile NCL (INCL), the most severe form of NCL, is caused by 
      mutations in the Ppt1 gene, which encodes the lysosomal enzyme palmitoyl-protein 
      thioesterase 1 (Ppt1). We generated mutations in the Ppt1 ortholog of Drosophila 
      melanogaster to characterize phenotypes caused by Ppt1 deficiency in flies. 
      Ppt1-deficient flies accumulate abnormal autofluorescent storage material 
      predominantly in the adult CNS and have a life span 30% shorter than wild type, 
      phenotypes that generally recapitulate disease-associated phenotypes common to 
      all forms of NCL. In contrast, some phenotypes of Ppt1-deficient flies differed 
      from those observed in human INCL. Storage material in flies appeared as highly 
      laminar spherical deposits in cells of the brain and as curvilinear profiles in 
      cells of the thoracic ganglion. This contrasts with the granular deposits 
      characteristic of human INCL. In addition, the reduced life span of 
      Ppt1-deficient flies is not caused by progressive death of CNS neurons. No 
      changes in brain morphology or increases in apoptotic cell death of CNS neurons 
      were detected in Ppt1-deficient flies, even at advanced ages. Thus, 
      Ppt1-deficient flies accumulate abnormal storage material and have a shortened 
      life span without evidence of concomitant neurodegeneration.
FAU - Hickey, Anthony J
AU  - Hickey AJ
AD  - Wadsworth Center, New York State Department of Health, Albany 12201-2002, USA.
FAU - Chotkowski, Heather L
AU  - Chotkowski HL
FAU - Singh, Navjot
AU  - Singh N
FAU - Ault, Jeffrey G
AU  - Ault JG
FAU - Korey, Christopher A
AU  - Korey CA
FAU - MacDonald, Marcy E
AU  - MacDonald ME
FAU - Glaser, Robert L
AU  - Glaser RL
LA  - eng
GR  - R01 NS033648/NS/NINDS NIH HHS/United States
GR  - R21 NS044572/NS/NINDS NIH HHS/United States
GR  - NS33648/NS/NINDS NIH HHS/United States
GR  - NS44572/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060201
PL  - United States
TA  - Genetics
JT  - Genetics
JID - 0374636
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Disease Models, Animal
MH  - Drosophila melanogaster/*genetics/physiology
MH  - Female
MH  - Male
MH  - Microscopy, Electron
MH  - Microscopy, Fluorescence
MH  - Mutation
MH  - Neurodegenerative Diseases/metabolism
MH  - Neuronal Ceroid-Lipofuscinoses/metabolism
MH  - Neurons/metabolism
MH  - Phenotype
MH  - RNA Interference
MH  - Thiolester Hydrolases/*genetics/*physiology
PMC - PMC1456391
EDAT- 2006/02/03 09:00
MHDA- 2006/07/18 09:00
PMCR- 2006/07/01
CRDT- 2006/02/03 09:00
PHST- 2006/02/03 09:00 [pubmed]
PHST- 2006/07/18 09:00 [medline]
PHST- 2006/02/03 09:00 [entrez]
PHST- 2006/07/01 00:00 [pmc-release]
AID - genetics.105.053306 [pii]
AID - gen17242379 [pii]
AID - 10.1534/genetics.105.053306 [doi]
PST - ppublish
SO  - Genetics. 2006 Apr;172(4):2379-90. doi: 10.1534/genetics.105.053306. Epub 2006 
      Feb 1.