title: Transgenic expression of ZBP1 in neurons suppresses cocaine-associated conditioning.
abstract: To directly address whether regulating mRNA localization can influence animal behavior, we created transgenic mice that conditionally express Zipcode Binding Protein 1 (ZBP1) in a subset of neurons in the brain. ZBP1 is an RNA-binding protein that regulates the localization, as well as translation and stability of target mRNAs in the cytoplasm. We took advantage of the absence of ZBP1 expression in the mature brain to examine the effect of expressing ZBP1 on animal behavior. We constructed a transgene conditionally expressing a GFP-ZBP1 fusion protein in a subset of forebrain neurons and compared cocaine-cued place conditioning in these mice versus noninduced littermates. Transgenic ZBP1 expression resulted in impaired place conditioning relative to nonexpressing littermates, and acutely repressing expression of the transgene restored normal cocaine conditioning. To gain insight into the molecular changes that accounted for this change in behavior, we identified mRNAs that specifically immunoprecipitated with transgenic ZBP1 protein from the brains of these mice. These data suggest that RNA-binding proteins can be used as a tool to identify the post-transcriptional regulation of gene expression in the establishment and function of neural circuits involved in addiction behaviors.
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461-1975, USA.
authors.forename: Kyle A B
authors.initials: KA
authors.lastname: Lapidus
authors.forename: Chiso
authors.initials: C
authors.lastname: Nwokafor
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Baroni
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tenenbaum
authors.forename: Noboru
authors.initials: N
authors.lastname: Hiroi
authors.forename: Robert H
authors.initials: RH
authors.lastname: Singer
authors.forename: Kevin
authors.initials: K
authors.lastname: Czaplinski
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C485731:ZBP1 protein, human; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D003042:Cocaine; D004318:Doxycycline