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2010 | 70 | 3 |
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Direct gene transfer in the Göttingen minipig CNS using stereotaxic lentiviral microinjections

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We aim to induce direct viral mediated gene transfer in the substantia nigra (SN) of the Göttingen minipig using MRI guided stereotaxic injections of lentiviral vectors encoding enhanced green fluorescent protein (EGFP). Nine female Göttingen minipigs were injected unilaterally into the SN with 6×2.5 μl lentivirus capable of transducing cells and mediating expression of recombinant EGFP. The animals were euthanized after four (n=3) or twenty weeks (n=6). Fresh brain tissue from three animals was used for PCR. The remaining six brains were cryo- or paraffin-sectioned for fluorescence, Nissl-, and immunohistochemical EGFP visualization. EGFP was seen in nigral neurons, axons, glial cells, endothelial cells, and in nigral fibers targeting the striatum. PCR-based detection confirmed the presence of the transgene in SN, whereas all other examined brain areas were negative, indicating that the immunohistochemically detected EGFP in the striatum derived from transfected nigral cells.
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  • Faculty of Health Sciences, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark
  • Faculty of Agricultural Sciences, Department of Genetics and Biotechnology, University of Aarhus, DK-8830 Tjele, Denmark
  • Faculty of Health Sciences, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark
  • Department of Neurosurgery, Aarhus University Hospital, DK-8000 Aarhus C, Denmark
  • Faculty of Agricultural Sciences, Department of Genetics and Biotechnology, University of Aarhus, DK-8830 Tjele, Denmark
  • Faculty of Health Sciences, Institute of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark
  • Faculty of Agricultural Sciences, Department of Genetics and Biotechnology, University of Aarhus, DK-8830 Tjele, Denmark
  • Faculty of Health Sciences, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark
  • Department of Neurosurgery, Aarhus University Hospital, DK-8000 Aarhus C, Denmark
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