Developmental expression of palmitoyl protein thioesterase in normal mice

Deficiency in palmitoyl protein thioesterase (PPT) results in the rapid dea th of neocortical neurons in human. Very little is known about the developm ental and cell-specific expression of this lysosomal enzyme. Here we show t hat PPT is expressed as a major 2.65 kb and a minor 1.85 kb transcript in t he mouse brain. Transcript levels gradually increase between postnatal days 10 and 30. In situ hybridization analysis revealed that PPT transcripts ar e found widely but nor homogeneously in the brain. The most intense signal was detected in the cerebral cortex (layers II, IV-V), hippocampal CA1-CA3 pyramidal cells, dentate gyrus granule cells and the hypothalamus. Immunost aining of PPT was localized in the cell soma, axons and dendrites, especial ly in the pyramidal and granular cells of the hippocampus, correlating well , both spatially and temporally, with the immunoreactivity of a presynaptic vesicle membrane protein, synaptophysin. In whole embryos, at embryonic da y 8, the PPT mRNA expression was most apparent throughout the neuroepitheli um. and from day 9 onwards it was seen in all tissues. The expression patte rn of PPT suggests its general significance for the brain cells and reflect s the response to maturation and growth of the neural networks. Strong PPT immunoreactivity in the axons and dentrites would imply that PPT may not be exclusively a lysosomal enzyme. A notable correlation with synaptophysin w ould suggest that PPT may have a role in the function of the synaptic machi nery. (C) 1999 Elsevier Science B.V. All rights reserved.