Synthetic microRNA-mediated downregulation of Nogo-A in transgenic rats reveals its role as regulators of synaptiv plasticity and cognitive function
Authors: Tews B, Schönig K, Arzta ME, Clementic S, Rioult-Pedotti M-S, Zemmara A, Bergerc SM, Schneider M, Enkel T, Weinmann O, Kaspera H-J, Schwaba ME, Bartsch D
CellNetworks People: Tews Björn
Journal: Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6583-8. doi: 10.1073/pnas.1217665110

We have generated a transgenic ratmodel using RNAi and used it to study the role of themembrane protein Nogo-A in synaptic plasticity and cognition. The membrane protein Nogo-A is expressed in CNS oligodendrocytes and subpopulations of neurons, and it is known to suppress neurite growth and regeneration. The constitutively expressed polymerase II-driven transgenewas composed of a micro- RNA-targeting Nogo-A placed into an intron preceding the coding sequence for EGFP, thus quantitatively labeling cells according to intracellular microRNA expression. The transgenic microRNA in vivo efficiently reduced the concentration of Nogo-A mRNA and protein preferentially in neurons. The resulting significant increase in longterm potentiation in both hippocampus and motor cortex indicates a repressor function of Nogo-A in synaptic plasticity. The transgenic rats exhibited prominent schizophrenia-like behavioral phenotypes, such as perseveration, disrupted prepulse inhibition, and strong withdrawal from social interactions. This fast and efficient micro- RNA-mediated knockdown provides a way to silence gene expression in vivo in transgenic rats and shows a role of Nogo-A in regulating higher cognitive brain functions.