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Polymorphic GGC repeat differentially regulates human reelin gene expression levels

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Summary.

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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  1. Laboratory of Molecular Psychiatry and Neurogenetics, University “Campus Bio-Medico”, Rome, Italy

    A. M. Persico

  2. I.R.C.C.S. “Fondazione S. Lucia”, Rome, Italy

    A. M. Persico

  3. Vanderbilt Kennedy Center for Research on Human Development and Department of Pharmacology, Vanderbilt University, Nashville, TN, USA

    P. Levitt & A. F. Pimenta

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Persico, A., Levitt, P. & Pimenta, A. Polymorphic GGC repeat differentially regulates human reelin gene expression levels. J Neural Transm 113, 1373–1382 (2006). https://doi.org/10.1007/s00702-006-0441-6

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