title: A comparative analysis of constitutive and cell-specific promoters in the adult mouse hippocampus using lentivirus vector-mediated gene transfer.
abstract: BACKGROUND
  Viral vectors provide powerful tools for transgene delivery to the mammalian brain to assess the effects of therapeutic proteins, antisense RNAs or small interfering RNAs. A key advantage of such approaches is that specific brain regions implicated in a particular disease can be independently targeted.
  
  
  METHODS
  To optimize transgene expression in sub-regions of the mouse hippocampus and with a view towards devising gene therapy strategies for Alzheimer's disease, we designed lentivirus-based reporter vectors bearing various promoters, including constitutive and cell-specific promoters. Furthermore, we devised methods allowing a side-by-side comparison of transgene expression levels in neural cells both in vitro and in vivo.
  
  
  RESULTS
  Following stereotaxic injection into the adult mouse hippocampus, titer-adjusted lentiviral vectors bearing constitutive promoters resulted in robust and sub-region-specific transgene expression. Our results show that the human CMV-IE promoter resulted in efficient transgene expression in the entire hippocampus whereas transgene expression mediated by the hybrid hEF1alpha/HTLV promoter was limited mainly in the dentate gyrus and the CA2/3 region. Finally, the neuron-specific human synapsin I promoter was particularly effective in the dentate gyrus.
  
  
  CONCLUSIONS
  These findings indicate that subregion-specific transgene expression in the hippocampus can be achieved following lentivirus vector-mediated gene transfer.
authors.affiliation: Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kuroda
authors.forename: Robert H
authors.initials: RH
authors.lastname: Kutner
authors.forename: Nicolas G
authors.initials: NG
authors.lastname: Bazan
authors.forename: Jakob
authors.initials: J
authors.lastname: Reiser
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D019076:Transgenes