A novel adenoviral vector-mediated neuronal selective gene expression in neonatal mouse brain in response to hypoxia: Neurosci.Lett.

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TypeArticle
Journal titleNeurosci.Lett.
Volume419
Issue1
Pages2327; # of pages: 5
Subjectadministration & dosage; Animals; Animals,Newborn; Anoxia; Antibodies; antibody; assay; Brain; Canada; cell; Cell Line,Transformed; CELLS; Cytomegalovirus; DISEASE; EXPRESSION; GENE; Gene Expression; Gene Transfer Techniques; Genetic Vectors; genetics; Glial Fibrillary Acidic Protein; Humans; In Vitro; Ischemia; Laboratories; Luciferases; MECHANISMS; metabolism; Mice; Mice,Inbred C57BL; Neuroglia; Neurons; pathology; Phosphopyruvate Hydratase; physiology; physiopathology; POTENTIAL; Repressor Proteins; selective; SERIES; TARGET; therapy; Transcription Factors
AbstractSelective gene expression targeting neurons is a challenge, which, if successfully overcome, carries an enormous potential for clinical applications in therapeutics against neurodegenerative diseases. We have reported previously the construction of a series of adenoviral vectors capable of selectively expressing a reporter gene luciferase in cultured neurons [D. Huang, A. Desbois, S.T. Hou, A novel adenoviral vector which mediates hypoxia-inducible gene expression selectively in neurons, Gene Ther. 12 (2005) 1369-1376]. A combination of neuron restrictive silencer elements (NRSEs), hypoxia responsive elements (HREs) and CMV minimal promoter (CMVmp) was packaged into replication defective adenovirus to target gene expression selectively in neurons in a hypoxia-regulated manner. In the present study, we injected the adenoviral vectors into the neonatal mouse brain followed by treatment with hypoxia. The expression of the reporter luciferase gene was examined by luciferase assay and fluorescent immunostaining. Neurons and glial cells were identified by staining with antibodies against NeuN and GFAP, respectively. Remarkably, in response to hypoxia, Ad/5HRE-3NRSE showed strong hypoxia-inducible gene expression of the reporter luciferase selectively in neurons but not in glial cells. In contrast, brains infected with the control vector Ad/5HRE showed no selectivity in luciferase expression (in both neurons and glial cells) under the hypoxic condition. Taken together, these studies demonstrated that this vector (Ad/5HRE-3NRSE) can mediate gene expression selectively in neurons both in vitro and in vivo, supporting the suggestion that further refinement of this vector may lead to the development of a useful tool to investigate mechanisms of neuronal damage following cerebral ischemia and a possible effective gene therapy vector to stroke
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberHOU2007
NPARC number9371231
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Record identifier41b6d5f6-939e-498e-9fd1-b1c54b613aec
Record created2009-07-10
Record modified2016-05-09
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