title: Neuronal-specific and nerve growth factor-inducible expression directed by the preprotachykinin-A promoter delivered by an adeno-associated virus vector.
abstract: The ability to manipulate the expression of genes within neurons provides unique opportunities to study the role of individual gene products in nervous system function. Virus vectors are a potentially rapid tool for the experimental manipulation of gene expression in the mammalian nervous system. However, a block to the use of virus vector systems in neurobiology is often the lack of cell-specific expression of the gene within the nervous system, and the immune and inflammatory responses to both the virus vector and the delivered gene. We have generated an adeno-associated virus vector that exploits the restricted expression pattern of the rat preprotachykinin-A promoter to support reporter gene expression. We demonstrate that this virus has a neuronal-specific expression pattern. Moreover, it is shown for the first time that the proximal rat preprotachykinin-A promoter is nerve growth factor inducible. This virus will be a useful tool to (i) modify neuronal phenotype by expressing therapeutic molecules or antisense nucleic acid and (ii) dissect the signal transduction pathways that regulate promoter function in vivo.
authors.affiliation: Department of Veterinary Pathology, The University of Edinburgh, Summerhall, UK.
authors.forename: P T
authors.initials: PT
authors.lastname: Harrison
authors.forename: R G
authors.initials: RG
authors.lastname: Dalziel
authors.forename: N A
authors.initials: NA
authors.lastname: Ditchfield
authors.forename: J P
authors.initials: JP
authors.lastname: Quinn
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D000229:Dependovirus; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D009414:Nerve Growth Factors / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis; D015320:Tachykinins / Q000235:genetics*; D014162:Transfection / Q000379:methods
chemical_list: D009414:Nerve Growth Factors; D011498:Protein Precursors; D011994:Recombinant Proteins; D015320:Tachykinins; C044206:preprotachykinin; D008156:Luciferases