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Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9

Author

Listed:
  • Malin Åkerblom

    (Lab of Molecular Neurogenetics, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University)

  • Rohit Sachdeva

    (Lab of Molecular Neurogenetics, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University)

  • Luis Quintino

    (CNS Gene Therapy Unit, Wallenberg Neuroscience Center, Lund University)

  • Erika Elgstrand Wettergren

    (CNS Gene Therapy Unit, Wallenberg Neuroscience Center, Lund University)

  • Katie Z. Chapman

    (Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital)

  • Giuseppe Manfre

    (CNS Gene Therapy Unit, Wallenberg Neuroscience Center, Lund University)

  • Olle Lindvall

    (Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital)

  • Cecilia Lundberg

    (CNS Gene Therapy Unit, Wallenberg Neuroscience Center, Lund University)

  • Johan Jakobsson

    (Lab of Molecular Neurogenetics, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University)

Abstract

Functional studies of resident microglia require molecular tools for their genetic manipulation. Here we show that microRNA-9-regulated lentiviral vectors can be used for the targeted genetic modification of resident microglia in the rodent brain. Using transgenic reporter mice, we demonstrate that murine microglia lack microRNA-9 activity, whereas most other cells in the brain express microRNA-9. Injection of microRNA-9-regulated vectors into the adult rat brain induces transgene expression specifically in cells with morphological features typical of ramified microglia. The majority of transgene-expressing cells colabels with the microglia marker Iba1. We use this approach to visualize and isolate activated resident microglia without affecting circulating and infiltrating monocytes or macrophages in an excitotoxic lesion model in rat striatum. The microRNA-9-regulated vectors described here are a straightforward and powerful tool that facilitates functional studies of resident microglia.

Suggested Citation

  • Malin Åkerblom & Rohit Sachdeva & Luis Quintino & Erika Elgstrand Wettergren & Katie Z. Chapman & Giuseppe Manfre & Olle Lindvall & Cecilia Lundberg & Johan Jakobsson, 2013. "Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9," Nature Communications, Nature, vol. 4(1), pages 1-8, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2801
    DOI: 10.1038/ncomms2801
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    Cited by:

    1. Rouven Schulz & Medina Korkut-Demirbaş & Alessandro Venturino & Gloria Colombo & Sandra Siegert, 2022. "Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses," Nature Communications, Nature, vol. 13(1), pages 1-26, December.

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