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Tackling Tissue Macrophage Heterogeneity by SplitCre Transgenesis

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Tissue-Resident Macrophages

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2713))

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Abstract

Macrophages represent a broad spectrum of distinct, but closely related tissue-resident immune cells. This presents a major challenge for the study of functional aspects of these cells using classical Cre recombinase-mediated conditional mutagenesis in mice, since single promoter-driven Cre transgenic models often display limited specificity toward their intended target. The advent of CRISPR/Cas9 technology has now provided a time- and cost-effective method to explore the full potential of binary transgenic, intersectional genetics. Specifically, the use of two promoters driving inactive Cre fragments that, when co-expressed, dimerize and only then gain recombinase activity allows the characterization and manipulation of genetically defined tissue macrophage subpopulations. Here, we will elaborate on the use of this protocol to capitalize on these recent technological advances in mouse genetics and discuss their strengths and pitfalls to improve the study of tissue macrophage subpopulations in physiology and pathophysiology.

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Acknowledgments

We would like to thank Johannes Hirrlinger, Leipzig University, Germany, for sharing reagents and advice. We thank the members of the Jung laboratory for helpful discussions. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 259373024—TRR 167 (NeuroMac), the American Brain Foundation, the Roland N. Karlen Foundation, the Blythe Brenden-Mann Foundation, and the Estate of David Levinson. S. Jung is the Incumbent of the Henry. H. Drake Professional Chair of Immunology.

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  1. Sigalit Boura-Halfon, Rebecca Haffner-Krausz and Shifra Ben-Dor contributed equally.

Authors and Affiliations

  1. Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel

    Sigalit Boura-Halfon, Jung-Seok Kim & Steffen Jung

  2. Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel

    Rebecca Haffner-Krausz

  3. Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel

    Shifra Ben-Dor

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  1. Sigalit Boura-Halfon
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  4. Jung-Seok Kim
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  5. Steffen Jung
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Correspondence to Sigalit Boura-Halfon or Steffen Jung .

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  1. Life & Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany

    Elvira Mass

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Boura-Halfon, S., Haffner-Krausz, R., Ben-Dor, S., Kim, JS., Jung, S. (2024). Tackling Tissue Macrophage Heterogeneity by SplitCre Transgenesis. In: Mass, E. (eds) Tissue-Resident Macrophages. Methods in Molecular Biology, vol 2713. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3437-0_32

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  • DOI: https://doi.org/10.1007/978-1-0716-3437-0_32

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