PMID- 11717424
OWN - NLM
STAT- MEDLINE
DCOM- 20020108
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 24
DP  - 2001 Nov 20
TI  - Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout 
      mice.
PG  - 13566-71
AB  - PPT1 and PPT2 encode two lysosomal thioesterases that catalyze the hydrolysis of 
      long chain fatty acyl CoAs. In addition to this function, PPT1 (palmitoyl-protein 
      thioesterase 1) hydrolyzes fatty acids from modified cysteine residues in 
      proteins that are undergoing degradation in the lysosome. PPT1 deficiency in 
      humans causes a neurodegenerative disorder, infantile neuronal ceroid 
      lipofuscinosis (also known as infantile Batten disease). In the current work, we 
      engineered disruptions in the PPT1 and PPT2 genes to create "knockout" mice that 
      were deficient in either enzyme. Both lines of mice were viable and fertile. 
      However, both lines developed spasticity (a "clasping" phenotype) at a median age 
      of 21 wk and 29 wk, respectively. Motor abnormalities progressed in the PPT1 
      knockout mice, leading to death by 10 mo of age. In contrast, the majority of 
      PPT2 mice were alive at 12 mo. Myoclonic jerking and seizures were prominent in 
      the PPT1 mice. Autofluorescent storage material was striking throughout the 
      brains of both strains of mice. Neuronal loss and apoptosis were particularly 
      prominent in PPT1-deficient brains. These studies provide a mouse model for 
      infantile neuronal ceroid lipofuscinosis and further suggest that PPT2 serves a 
      role in the brain that is not carried out by PPT1.
FAU - Gupta, P
AU  - Gupta P
AD  - The Hamon Center for Therapeutic Oncology Research, University of Texas 
      Southwestern Medical Center, Dallas, TX 75390, USA.
FAU - Soyombo, A A
AU  - Soyombo AA
FAU - Atashband, A
AU  - Atashband A
FAU - Wisniewski, K E
AU  - Wisniewski KE
FAU - Shelton, J M
AU  - Shelton JM
FAU - Richardson, J A
AU  - Richardson JA
FAU - Hammer, R E
AU  - Hammer RE
FAU - Hofmann, S L
AU  - Hofmann SL
LA  - eng
GR  - N01NS32353/NS/NINDS NIH HHS/United States
GR  - R01 NS036867/NS/NINDS NIH HHS/United States
GR  - R37 NS036867/NS/NINDS NIH HHS/United States
GR  - NS36867/NS/NINDS NIH HHS/United States
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  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Animals
MH  - Female
MH  - Gene Targeting
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuronal Ceroid-Lipofuscinoses/*enzymology/pathology
MH  - Phenotype
MH  - Thiolester Hydrolases/genetics/*physiology
PMC - PMC61081
EDAT- 2001/11/22 10:00
MHDA- 2002/01/10 10:01
PMCR- 2002/05/20
CRDT- 2001/11/22 10:00
PHST- 2001/11/22 10:00 [pubmed]
PHST- 2002/01/10 10:01 [medline]
PHST- 2001/11/22 10:00 [entrez]
PHST- 2002/05/20 00:00 [pmc-release]
AID - 98/24/13566 [pii]
AID - 251485198 [pii]
AID - 4851 [pii]
AID - 10.1073/pnas.251485198 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13566-71. doi: 
      10.1073/pnas.251485198.