PDGFRβ-P2A-CreERT2 mice: a genetic tool to target pericytes in angiogenesis
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Pericytes are essential mural cells distinguished by their association with small caliber blood vessels and the presence of a basement membrane shared with endothelial cells. Pericyte interaction with the endothelium plays an important role in angiogenesis; however, very few tools are currently available that allow for the targeting of pericytes in mouse models, limiting our ability to understand their biology. We have generated a novel mouse line expressing tamoxifen-inducible Cre-recombinase under the control of the platelet-derived growth factor receptor β promoter: PDGFRβ-P2A-CreER T2 . We evaluated the expression of the PDGFRβ-P2A-CreER T2 line by crossing it with fluorescent reporter lines and analyzed reporter signal in the angiogenic retina and brain at different time points after tamoxifen administration. Reporter lines showed labeling of NG2+, desmin+, PDGFRβ+ perivascular cells in the retina and the brain, indicating successful targeting of pericytes; however, signal from reporter lines was also observed in a small subset of glial cells both in the retina and the brain. We also evaluated recombination in tumors and found efficient recombination in perivascular cells associated with tumor vasculature. As a proof of principle, we used our newly generated driver to delete Notch signaling in perivascular cells and observed a loss of smooth muscle cells in retinal arteries, consistent with previously published studies evaluating Notch3 null mice. We conclude that the PDGFRβ-P2A-CreER T2 line is a powerful new tool to target pericytes and will aid the field in gaining a deeper understanding of the role of these cells in physiological and pathological settings.
KeywordsMural cells Pericytes Mouse models Platelet-derived growth factor β
We would like to thank Valeriya Borisenko for her assistance in mouse husbandry, and Hui-Chuan Hung for her assistance in the microinjection to generate the germline chimera and mouse breeding. This work was funded by NIH Grant R01HL112626 (J.K.), and NCI P30CA013696-40 (C.S.L).
C-SL, ML, and JK conceptualized and designed the PDGFRβ-P2A-CreER T2 mice. ML generated the PDGFRβ-P2A-CreERT2 targeting vector. FL performed the gene targeting and identified the targeted ES cells for the generation of the PDGFRβ-P2A-CreER T2 mice. HC, BP, and TN collected and interpreted the data on the characterization of the PDGFRβ-P2A-CreER T2 with the two reporter mouse lines. HC drafted the manuscript.
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Conflict of interest
The authors declare no conflict of interest.
Human and animal rights
This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted as described above.
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