Visualization and genetic modification of residentbrain microglia using lentiviral vectors regulatedby microRNA-9

摘要

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 targetedgenetic 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 inthe brain express microRNA-9. Injection of microRNA-9-regulated vectors into the adult ratbrain induces transgene expression specifically in cells with morphological features typical oframified microglia. The majority of transgene-expressing cells colabels with the microgliamarker Iba1. We use this approach to visualize and isolate activated resident microgliawithout affecting circulating and infiltrating monocytes or macrophages in an excitotoxiclesion model in rat striatum. The microRNA-9-regulated vectors described here are astraightforward and powerful tool that facilitates functional studies of resident microglia.