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Polymorphic GGC repeat differentially regulates human reelin gene expression levels.

A M Persico·P Levitt·A F Pimenta
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Abstract

The human gene encoding Reelin (RELN), a pivotal protein in neurodevelopment, includes a polymorphic GGC repeat in its 5' untranslated region (UTR). CHO cells transfected with constructs encompassing the RELN 5'UTR with 4-to-13 GGC repeats upstream of the luciferase reporter gene show declining luciferase activity with increasing GGC repeat number (P < 0.005), as predicted by computer-based simulations. Conversely, RELN 5'UTR sequences boost reporter gene expression above control levels in neuronal SN56 and N2A cell lines, but 12- and 13-repeat alleles still yield 50-60% less luciferase activity compared to the more common 8- and 10-repeat alleles (P < 0.0001). RELN "long" GGC alleles significantly blunt gene expression and may, through this effect, confer vulnerability to human disorders, such as schizophrenia and autism.

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5' Untranslated RegionsAnimalsCHO CellsCell Adhesion Molecules, NeuronalCell LineCricetinaeCricetulusExtracellular Matrix ProteinsFibroblastsGene ExpressionGene Expression RegulationGenes, ReporterHumansNerve Tissue ProteinsNeuronsPolymorphism, GeneticRNA, MessengerReelin ProteinSerine EndopeptidasesTransfectionTrinucleotide RepeatsComparative StudyJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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BibTeXRIS

A M Persico, P Levitt, A F Pimenta. 2006-04-11. Polymorphic GGC repeat differentially regulates human reelin gene expression levels.. https://doi.org/10.1007/s00702-006-0441-6

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