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

Malin Åkerblom, Rohit Sachdeva, Luis Quintino, Erika Elgstrand Wettergren, Katie Z. Chapman, Giuseppe Manfre, Olle Lindvall, Cecilia Lundberg and Johan Jakobsson ()
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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

Nature Communications, 2013, vol. 4, issue 1, 1-8

Abstract: 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.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2801

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DOI: 10.1038/ncomms2801

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