Transgenic Targeting of Fcrls Creates a Highly Efficient Constitutively Active Microglia Cre Line with Differentiated Specificity
Name
ENEURO.0549-23.2024.full.pdf
Description
Published version
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6.13 MB
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Author(s)
Kaiser, Tobias
Dattero, Jordan
Li, Liang
Chen, Mandy
Jiang, Minqing
Harrahill, Andrew
Butovsky, Oleg
Feng, Guoping
Date Issued
July 2024
Journal
eNeuro
Publisher
Society for Neuroscience
Citation
Tobias Kaiser, Jordan Dattero, Liang Li, Mandy Chen, Minqing Jiang, Andrew Harrahill, Oleg Butovsky, Guoping Feng
eNeuro 26 June 2024, 11 (7) ENEURO.0549-23.2024.
Version
Final published version
Abstract
Microglia carry out important functions as the resident macrophages of the brain. To study their role in health and disease, the research community needs tools to genetically modify them with maximum completeness in a manner that distinguishes them from closely related cell types, such as monocytes. While currently available tamoxifen-inducible CreERT2 lines can achieve the differentiation from other cells, the field needs improved and publicly available constitutively active Cre lines, especially ones with favorable efficiency and specificity profiles for studies where high recombination efficiency is imperative and where tamoxifen administration is contraindicated. Here, we leverage the microglia-specific Fcrls gene to generate mice expressing Cre. Using genomic methods, we show correct positioning of the transgene and intact microglia homeostasis in Fcrls-2A-Cre mice. Crossing Fcrls-2A-Cre mice to four different reporters, we demonstrate highly efficient recombination in microglia across differentially sensitive loxP alleles in different genomic contexts, indicating robust applicability of the line. Further, we show that microglia recombine a loxP reporter during early embryonic development, supporting the use of the line for developmental studies. Finally, using immunofluorescence and flow cytometry, we reveal that most border-associated macrophages are also targeted whereas only few liver and spleen macrophages and virtually no white blood cell subsets exhibit Cre activity, distinguishing this line from another publicly available Cre line, Cx3cr1-CreM. Fcrls-2A-Cre mice are immediately available (JAX #036591) and serve as a valuable addition to the community's microglia toolbox by providing highly efficient constitutive Cre activity with excellent specificity, particularly for studies where tamoxifen administration is undesirable.
MIT Department
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
Broad Institute of MIT and Harvard
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DOI of Published Version
https://doi.org/10.1523/ENEURO.0549-23.2024
