Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo
説明
<jats:title>Abstract</jats:title><jats:p>Here we describe the microglia-targeting adeno-associated viral (AAV) vectors containing a 1.7-kb putative promoter region of microglia/macrophage-specific ionized calcium-binding adaptor molecule 1 (<jats:italic>Iba1</jats:italic>), along with repeated miRNA target sites for microRNA (miR)-9 and miR-129-2-3p. The 1.7-kb genomic sequence upstream of the start codon in exon 1 of the <jats:italic>Iba1</jats:italic> (<jats:italic>Aif1</jats:italic>) gene, functions as microglia preferential promoter in the striatum and cerebellum. Furthermore, ectopic transgene expression in non-microglial cells is markedly suppressed upon adding two sets of 4-repeated miRNA target sites for miR-9 and miR-129-2-3p, which are expressed exclusively in non-microglial cells and sponged AAV-derived mRNAs. Our vectors transduced ramified microglia in healthy tissues and reactive microglia in lipopolysaccharide-treated mice and a mouse model of neurodegenerative disease. Moreover, live fluorescent imaging allowed the monitoring of microglial motility and intracellular Ca<jats:sup>2+</jats:sup> mobilization. Thus, microglia-targeting AAV vectors are valuable for studying microglial pathophysiology and therapies, particularly in the striatum and cerebellum.</jats:p>
収録刊行物
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- Communications Biology
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Communications Biology 5 (1), 1224-, 2022-11-11
Springer Science and Business Media LLC
