A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages
- PMID: 33333014
- DOI: 10.1016/j.immuni.2020.11.007
A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages
Abstract
The developmental and molecular heterogeneity of tissue macrophages is unravelling, as are their diverse contributions to physiology and pathophysiology. Moreover, also given tissues harbor macrophages in discrete anatomic locations. Functional contributions of specific cell populations can in mice be dissected using Cre recombinase-mediated mutagenesis. However, single promoter-based Cre models show limited specificity for cell types. Focusing on macrophages in the brain, we establish here a binary transgenic system involving complementation-competent NCre and CCre fragments whose expression is driven by distinct promoters: Sall1ncre: Cx3cr1ccre mice specifically target parenchymal microglia and compound transgenic Lyve1ncre: Cx3cr1ccre animals target vasculature-associated macrophages, in the brain, as well as other tissues. We imaged the respective cell populations and retrieved their specific translatomes using the RiboTag in order to define them and analyze their differential responses to a challenge. Collectively, we establish the value of binary transgenesis to dissect tissue macrophage compartments and their functions.
Keywords: Lyve1 BAM; RiboTag; binary transgenic; brain macrophages; intersectional genetics; meninges; microglia; perivascular macrophages; pia mater; split cre.
Copyright © 2020 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Interests The authors declare that they have no competing interests.
Similar articles
-
Comparative analysis of CreER transgenic mice for the study of brain macrophages: A case study.Eur J Immunol. 2020 Mar;50(3):353-362. doi: 10.1002/eji.201948342. Epub 2019 Dec 11. Eur J Immunol. 2020. PMID: 31762013
-
Split-Cre complementation restores combination activity on transgene excision in hair roots of transgenic tobacco.PLoS One. 2014 Oct 17;9(10):e110290. doi: 10.1371/journal.pone.0110290. eCollection 2014. PLoS One. 2014. PMID: 25329460 Free PMC article.
-
Tackling Tissue Macrophage Heterogeneity by SplitCre Transgenesis.Methods Mol Biol. 2024;2713:481-503. doi: 10.1007/978-1-0716-3437-0_32. Methods Mol Biol. 2024. PMID: 37639143
-
Diversity and function of brain-associated macrophages.Curr Opin Immunol. 2022 Jun;76:102181. doi: 10.1016/j.coi.2022.102181. Epub 2022 Apr 21. Curr Opin Immunol. 2022. PMID: 35462276 Review.
-
Microglial physiology: unique stimuli, specialized responses.Annu Rev Immunol. 2009;27:119-45. doi: 10.1146/annurev.immunol.021908.132528. Annu Rev Immunol. 2009. PMID: 19302036 Review.
Cited by
-
Imputing spatial transcriptomics through gene network constructed from protein language model.Commun Biol. 2024 Oct 5;7(1):1271. doi: 10.1038/s42003-024-06964-2. Commun Biol. 2024. PMID: 39369061 Free PMC article.
-
Resilience of dermis resident macrophages to inflammatory challenges.Exp Mol Med. 2024 Oct 1. doi: 10.1038/s12276-024-01313-z. Online ahead of print. Exp Mol Med. 2024. PMID: 39349826 Review.
-
The role of RNA modifications in disease-associated macrophages.Mol Ther Nucleic Acids. 2024 Aug 26;35(4):102315. doi: 10.1016/j.omtn.2024.102315. eCollection 2024 Dec 10. Mol Ther Nucleic Acids. 2024. PMID: 39296330 Free PMC article. Review.
-
Progress in Structural and Functional In Vivo Imaging of Microglia and Their Application in Health and Disease.Adv Neurobiol. 2024;37:65-80. doi: 10.1007/978-3-031-55529-9_5. Adv Neurobiol. 2024. PMID: 39207687 Review.
-
Visualization, Fate Mapping, Ablation, and Mutagenesis of Microglia in the Mouse Brain.Adv Neurobiol. 2024;37:53-63. doi: 10.1007/978-3-031-55529-9_4. Adv Neurobiol. 2024. PMID: 39207686
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous