RGD Reference Report - Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice. - Rat Genome Database

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Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice.

Authors: Gupta, P  Soyombo, AA  Atashband, A  Wisniewski, KE  Shelton, JM  Richardson, JA  Hammer, RE  Hofmann, SL 
Citation: Gupta P, etal., Proc Natl Acad Sci U S A 2001 Nov 20;98(24):13566-71.
RGD ID: 734785
Pubmed: PMID:11717424   (View Abstract at PubMed)
PMCID: PMC61081   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.251485198   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Ppt1  (palmitoyl-protein thioesterase 1)
Ppt2  (palmitoyl-protein thioesterase 2)

Genes (Mus musculus)
Ppt1  (palmitoyl-protein thioesterase 1)
Ppt2  (palmitoyl-protein thioesterase 2)

Genes (Homo sapiens)
PPT1  (palmitoyl-protein thioesterase 1)
PPT2  (palmitoyl-protein thioesterase 2)

Objects referenced in this article
Gene Tpp1 tripeptidyl peptidase I Mus musculus
Gene Tpp1 tripeptidyl peptidase 1 Rattus norvegicus

Additional Information