title: Adenovector-mediated hair cell regeneration is affected by  promoter type.
abstract: CONCLUSIONS
  Replacement of vestibular hair cells induced by atoh1 driven by the tissue-specific GFAP promoter was significantly more efficient than use of the cBA or hCMV promoter.
  
  
  OBJECTIVE
  To test whether expression level, persistence, or selectivity from adenovirus vectors delivered in the inner ear can be altered by changing the adenovector backbone or by using different cellular and viral promoters.
  
  
  METHODS
  Adenovector and promoter modifications were tested for differences in transgene expression in adult macular organs. The effect of using an E1/E3 deleted vector was compared to E1/E3/E4 deleted vectors. The effect of using viral and cellular promoters to modify transgene expression was tested in explanted adult mouse macular organs. Based on these results three different promoters were tested for efficacy of atonal gene.
  
  
  RESULTS
  Use of adenovectors containing human CMV, the hybrid cBA and ubiquitin promoters driving transgene expression resulted in different types of transgene expression. While several viral and cellular promoters provided broad cell type expression, expression driven by the GFAP promoter was limited to vestibular supporting cells, demonstrating the specificity of this promoter.
authors.affiliation: Department of Otolaryngology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Praetorius
authors.forename: Chi
authors.initials: C
authors.lastname: Hsu
authors.forename: Kim
authors.initials: K
authors.lastname: Baker
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Brough
authors.forename: Peter
authors.initials: P
authors.lastname: Plinkert
authors.forename: Hinrich
authors.initials: H
authors.lastname: Staecker
mesh_terms: D008267:Acoustic Maculae / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000502:physiology; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018069:Hair Cells, Vestibular / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011401:Promoter Regions, Genetic / Q000235:genetics; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: D017500:Adenovirus E1A Proteins; D005904:Glial Fibrillary Acidic Protein; D014452:Ubiquitins; D049452:Green Fluorescent Proteins