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A Transgenic Line That Reports CSF1R Protein Expression Provides a Definitive Marker for the Mouse Mononuclear
Kathleen Grabert1, Anuj Sehgal2, Katharine M Irvine2
1The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH259RG, United Kingdom.
Journal of Immunology (Baltimore, Md. : 1950)
|November 3, 2020
Summary
Researchers developed a novel CSF1R reporter mouse to track mononuclear phagocyte system (MPS) cells. This tool precisely identifies MPS cells, revealing their abundance and distribution across various tissues.
Area of Science:
- Immunology
- Cell Biology
- Genetics
Background:
- The mononuclear phagocyte system (MPS) is crucial for cellular immunity and tissue homeostasis.
- Identifying universal and lineage-specific markers for MPS cells, including monocytes, macrophages, and dendritic cells, remains a challenge.
- The colony-stimulating factor 1 receptor (CSF1R) is a key regulator of MPS cell development and function.
Purpose of the Study:
- To develop and characterize a novel reporter mouse model for tracking CSF1R-expressing cells.
- To assess the specificity and utility of the CSF1R reporter for identifying MPS populations in vivo.
- To investigate the distribution and abundance of MPS cells in various tissues using the reporter system.
Main Methods:
- Generation of a CSF1R reporter mouse by inserting a FusionRed (FRed) fluorescent cassette into the CSF1R locus.
- In vitro and in vivo validation of CSF1R-FRed expression in different cell types and tissues.
- Comparative analysis of CSF1R-FRed expression with established markers and in combination with other reporters (e.g., Csf1r-EGFP).
- Whole-mount imaging and tissue section analysis to visualize MPS populations.
Main Results:
- The CSF1R-FRed reporter mouse was successfully generated without compromising CSF1R function.
- CSF1R-FRed expression was confirmed in monocytes, macrophages, classical dendritic cells, osteoclasts, and megakaryocytes, but not in granulocytes or lymphocytes.
- Reporter expression was absent in hematopoietic stem cells, suggesting no direct role in early myeloid commitment.
- Whole-mount imaging revealed widespread distribution of MPS cells, including novel macrophage populations in non-lymphoid tissues like tendons and skeletal muscle.
Conclusions:
- The CSF1R-FRed reporter mouse offers a highly specific tool for identifying and studying cells of the mononuclear phagocyte system.
- This reporter system facilitates the visualization of MPS cell abundance and distribution, including previously uncharacterized populations.
- The findings provide new insights into the tissue-specific roles and distribution of MPS cells in health and disease.
