A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages

Jung-Seok Kim, Masha Kolesnikov, Shany Peled-Hajaj, Isabelle Scheyltjens, Yuan Xia, Sebastien Trzebanski, Zhana Haimon, Anat Shemer, Alisa Lubart, Hannah Van Hove, Louise Chappell-Maor, Sigalit Boura-Halfon, Kiavash Movahedi, Pablo Blinder, Steffen Jung

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)176-190
Number of pages15
JournalImmunity
Volume54
Issue number1
Early online date11 Dec 2020
DOIs
Publication statusPublished - 12 Jan 2021

Bibliographical note

Copyright © 2020. Published by Elsevier Inc.

Keywords

  • Lyve1 BAM
  • RiboTag
  • binary transgenic
  • brain macrophages
  • intersectional genetics
  • meninges
  • microglia
  • perivascular macrophages
  • pia mater
  • split cre

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