title: Palmitoyl-protein thioesterase gene expression in the developing mouse brain and retina: implications for early loss of vision in infantile neuronal ceroid lipofuscinosis.
abstract: 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 functions. To gain insight into the temporal onset of these clinical manifestations, 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 brain during development. Our results show that both cDNA and protein sequences 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 development. Furthermore, the retinal expression of mPPT occurs much earlier and at a higher level than in the brain at all developmental stages investigated. Since many retinal and brain proteins are highly palmitoylated and depalmitoylation by PPT is essential for their effective recycling in the lysosomes, our results raise the possibility that inactivating mutations of the PPT gene, as occur in INCL, are likely to cause cellular accumulation of lipid-modified proteins in the retina earlier than in the brain. Consequently, the loss of vision occurs before the deterioration of brain functions in this disease.
authors.affiliation: Section on Developmental Genetics, Heritable Disorders Branch, NICHD, NIH, Bethesda, MD 20892-1830, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: A K
authors.initials: AK
authors.lastname: Mandal
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: C L
authors.initials: CL
authors.lastname: Keck
authors.forename: D B
authors.initials: DB
authors.lastname: Zimonjic
authors.forename: N C
authors.initials: NC
authors.lastname: Popescu
authors.forename: A B
authors.initials: AB
authors.lastname: Mukherjee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001766:Blindness / Q000201:enzymology / Q000235:genetics*; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002874:Chromosome Mapping; D018076:DNA, Complementary; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology / Q000235:genetics*; D012160:Retina / Q000196:embryology / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase