Neuronal-specific and nerve growth factor-inducible expression directed by the preprotachykinin-A promoter delivered by an adeno-associated virus vector.
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.
Harrison
P T
PT
Department of Veterinary Pathology, The University of Edinburgh, Summerhall, UK.
Dalziel
R G
RG
Ditchfield
N A
NA
Quinn
J P
JP
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
D009414:Nerve Growth Factors; D011498:Protein Precursors; D011994:Recombinant Proteins; D015320:Tachykinins; C044206:preprotachykinin; D008156:Luciferases