title: Suppression of nitric oxide (NO)-dependent behavior by double-stranded RNA-mediated silencing of a neuronal NO synthase gene.
abstract: We have used double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) to disrupt neuronal nitric oxide (NO) synthase (nNOS) gene function in the snail Lymnaea stagnalis and have detected a specific behavioral phenotype. The injection of whole animals with synthetic dsRNA molecules targeted to the nNOS-encoding mRNA reduces feeding behavior in vivo and fictive feeding in vitro and interferes with NO synthesis by the CNS. By showing that synthetic dsRNA targeted to the nNOS mRNA causes a significant and long-lasting reduction in the levels of Lym-nNOS mRNA, we verify that specific RNAi has occurred. Importantly, our results establish that the expression of nNOS gene is essential for normal feeding behavior. They also show that dsRNA can be used in the investigation of functional gene expression in the context of whole animal behavior, regardless of the availability of targeted mutation technologies.
authors.affiliation: Sussex Centre for Neuroscience, University of Sussex, Brighton BN1 9QG, United Kingdom.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Korneev
authors.forename: Ildiko
authors.initials: I
authors.lastname: Kemenes
authors.forename: Volko
authors.initials: V
authors.lastname: Straub
authors.forename: Kevin
authors.initials: K
authors.lastname: Staras
authors.forename: Elena I
authors.initials: EI
authors.lastname: Korneeva
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Kemenes
authors.forename: Paul R
authors.initials: PR
authors.lastname: Benjamin
authors.forename: Michael
authors.initials: M
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects* / Q000502:physiology; D018390:Gene Targeting / Q000379:methods; D066298:In Vitro Techniques; D008195:Lymnaea; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010641:Phenotype; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I