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

ABSTRACT: 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, lea

SUBMITTER: Gupta P 

PROVIDER: S-EPMC61081 | biostudies-literature | 2001 Nov

REPOSITORIES: biostudies-literature