title: Local knockdown of ERK2 in the adult mouse brain via adeno-associated virus-mediated RNA interference.
abstract: In recent years RNA interference (RNAi) has become a useful genetic tool to downregulate candidate disease genes for which pharmaceutical inhibitors are not available. In combination with viral vectors to trigger RNAi in the mammalian body, it allows the localized and specific manipulation of the expression of single or multiple genes in vivo. The MAP kinases ERK1 and ERK2 are involved in the transduction of extracellular signals to nuclear effectors. A role for ERKs has been proposed in the adult brain in mediating neuronal functions, as for fear learning in the lateral amygdala. To study the role of ERK in anxiety disorders characterized by disturbed fear learning processes we developed Erk-specific RNAi tools and tested the efficacy of a viral Erk2 vector in the adult mouse brain. We found shRNAs that showed silencing of either both ERK1/2 or only ERK2. In particular, our analysis showed that an Erk2-specific shRNA reduced the activity of this gene at comparable efficiency both in vitro and in vivo. This reagent provides a useful tool to study the role of ERK2, for which small molecule inhibitors are not available, in the development of anxiety and other psychiatric disorders.
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environment and Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg/Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Benedetto
authors.forename: Barbara Di
authors.initials: BD
authors.lastname: Benedetto
authors.forename: Benedikt
authors.initials: B
authors.lastname: Wefers
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Ralf
authors.initials: R
authors.lastname: Kühn
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000201:enzymology*; D000704:Analysis of Variance; D000818:Animals; D001008:Anxiety Disorders / Q000201:enzymology; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D055785:Gene Knockdown Techniques / Q000379:methods*; D005822:Genetic Vectors; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D034741:RNA, Small Interfering; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3