| Literature DB >> 32541832 |
Takahiro Masuda1,2, Lukas Amann3,4, Roman Sankowski3,5, Ori Staszewski3,5, Maximilian Lenz6, Paolo D Errico7,8, Nicolas Snaidero9, Marta Joana Costa Jordão3, Chotima Böttcher10, Katrin Kierdorf3,11,12, Steffen Jung13, Josef Priller10,14,15, Thomas Misgeld9,16,17, Andreas Vlachos6,11, Melanie Meyer-Luehmann7,8,11, Klaus-Peter Knobeloch3, Marco Prinz18,19,20.
Abstract
Microglia and central nervous system (CNS)-associated macrophages (CAMs), such as perivascular and meningeal macrophages, are implicated in virtually all diseases of the CNS. However, little is known about their cell-type-specific roles in the absence of suitable tools that would allow for functional discrimination between the ontogenetically closely related microglia and CAMs. To develop a new microglia gene targeting model, we first applied massively parallel single-cell analyses to compare microglia and CAM signatures during homeostasis and disease and identified hexosaminidase subunit beta (Hexb) as a stably expressed microglia core gene, whereas other microglia core genes were substantially downregulated during pathologies. Next, we generated HexbtdTomato mice to stably monitor microglia behavior in vivo. Finally, the Hexb locus was employed for tamoxifen-inducible Cre-mediated gene manipulation in microglia and for fate mapping of microglia but not CAMs. In sum, we provide valuable new genetic tools to specifically study microglia functions in the CNS.Entities:
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Year: 2020 PMID: 32541832 DOI: 10.1038/s41590-020-0707-4
Source DB: PubMed Journal: Nat Immunol ISSN: 1529-2908 Impact factor: 25.606