TY  - JOUR
AU  - Masuda, Takahiro
AU  - Amann, Lukas
AU  - Sankowski, Roman
AU  - Staszewski, Ori
AU  - Lenz, Maximilian
AU  - D Errico, Paolo
AU  - Snaidero, Nicolas
AU  - Costa Jordão, Marta Joana
AU  - Böttcher, Chotima
AU  - Kierdorf, Katrin
AU  - Jung, Steffen
AU  - Priller, Josef
AU  - Misgeld, Thomas
AU  - Vlachos, Andreas
AU  - Meyer-Luehmann, Melanie
AU  - Knobeloch, Klaus-Peter
AU  - Prinz, Marco
TI  - Novel Hexb-based tools for studying microglia in the CNS.
JO  - Nature immunology
VL  - 21
IS  - 7
SN  - 1529-2916
CY  - London
PB  - Springer Nature Limited
M1  - DZNE-2020-01365
SP  - 802 - 815
PY  - 2020
AB  - 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.
KW  - Animals
KW  - Brain: cytology
KW  - Brain: immunology
KW  - Brain: pathology
KW  - CRISPR-Cas Systems: genetics
KW  - Encephalomyelitis, Autoimmune, Experimental: immunology
KW  - Encephalomyelitis, Autoimmune, Experimental: pathology
KW  - Facial Nerve Injuries: immunology
KW  - Facial Nerve Injuries: pathology
KW  - Gene Knock-In Techniques
KW  - Genes, Reporter: genetics
KW  - Genetic Loci: genetics
KW  - Humans
KW  - Intravital Microscopy
KW  - Luminescent Agents: chemistry
KW  - Luminescent Proteins: chemistry
KW  - Luminescent Proteins: genetics
KW  - Macrophages: immunology
KW  - Macrophages: metabolism
KW  - Mice
KW  - Microglia: immunology
KW  - Microglia: metabolism
KW  - NIH 3T3 Cells
KW  - RNA-Seq
KW  - Single-Cell Analysis
KW  - Transfection
KW  - beta-Hexosaminidase beta Chain: genetics
KW  - beta-Hexosaminidase beta Chain: metabolism
KW  - Luminescent Agents (NLM Chemicals)
KW  - Luminescent Proteins (NLM Chemicals)
KW  - red fluorescent protein (NLM Chemicals)
KW  - beta-Hexosaminidase beta Chain (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32541832
DO  - DOI:10.1038/s41590-020-0707-4
UR  - https://pub.dzne.de/record/153368
ER  -