title: Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9.
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.
authors.affiliation: Lab of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund 221 84, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Åkerblom
authors.forename: Rohit
authors.initials: R
authors.lastname: Sachdeva
authors.forename: Luis
authors.initials: L
authors.lastname: Quintino
authors.forename: Erika Elgstrand
authors.initials: EE
authors.lastname: Wettergren
authors.forename: Katie Z
authors.initials: KZ
authors.lastname: Chapman
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Manfre
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lundberg
authors.forename: Johan
authors.initials: J
authors.lastname: Jakobsson
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005821:Genetic Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D011533:Proviruses / Q000235:genetics; D051381:Rats; D019076:Transgenes
chemical_list: C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs