Palmitoyl-protein thioesterase gene expression in the developing mouse brain and retina: Implications for early loss of vision in infantile neuronal ceroid lipofuscinosis

Mutations in the palmitoyl-protein thioesterase (PPT) gene cause infantile neuronal ceroid lipofuscinosis (INCL), the clinical manifestations of which include the early loss of vision followed by deterioration of brain functi ons. To gain insight into the temporal onset of these clinical manifestatio ns, we isolated and characterized a murine PPT (mPPT)-cDNA, mapped the gene on distal chromosome 4, and studied its expression in the eye and in the b rain during development. Our results show that both cDNA and protein sequen ces of the murine and human PPTs are virtually identical and that the mPPT expression in the retina and in the brain is temporally regulated during de velopment. Furthermore, the retinal expression of mPPT occurs much earlier and at a higher level than in the brain at all developmental stages investi gated. Since many retinal and brain proteins are highly palmitoylated and d epalmitoylation by PPT is essential for their effective recycling in the ly sosomes, our results raise the possibility that inactivating mutations of t he PPT gene, as occur in INCL, are likely to cause cellular accumulation of lipid-modified proteins in the retina earlier than in the brain. Consequen tly, the loss of vision occurs before the deterioration of brain functions in this disease. (C) 1999 Elsevier Science B.V. All rights reserved.