Abstract
In the central nervous system (CNS) platelet derived growth factor receptor alpha (PDGFRα) is expressed exclusively by oligodendrocyte progenitor cells (OPCs), making the Pdgfrα promoter an ideal tool for directing transgene expression in this cell type. Two Pdgfrα-CreERT2 mouse lines have been generated for this purpose which, when crossed with cre-sensitive reporter mice, allow the temporally restricted labelling of OPCs for lineage-tracing studies. These mice have also been used to achieve the deletion of CNS-specific genes from OPCs. However the ability of Pdgfrα-CreERT2 mice to induce cre-mediated recombination in PDGFRα+ cell populations located outside of the CNS has not been examined. Herein we quantify the proportion of PDGFRα+ cells that become YFP-labelled following Tamoxifen administration to adult Pdgfrα-CreERT2::Rosa26-YFP transgenic mice. We report that the vast majority (>90%) of PDGFRα+ OPCs in the CNS, and a significant proportion of PDGFRα+ stromal cells within the bone marrow (~38%) undergo recombination and become YFP-labelled. However, only a small proportion of the PDGFRα+ cell populations found in the sciatic nerve, adrenal gland, pituitary gland, heart, gastrocnemius muscle, kidney, lung, liver or intestine become YFP-labelled. These data suggest that Pdgfrα-CreERT2 transgenic mice can be used to achieve robust recombination in OPCs, while having a minimal effect on most PDGFRα+ cell populations outside of the CNS.
Highlights
The platelet-derived growth factor receptor (PDGFR) was first identified in 1982, as a protein expressed by fibroblasts and arterial smooth muscle cells [1]
We report that PdgfrαCreERT2 transgenic mice are highly suitable for oligodendrocyte progenitor cells (OPCs)-directed gene recombination in the central nervous system (CNS), can be used to achieve robust recombination in OPCs, induce moderate recombination in PDGFRα+ bone marrow stromal cells, and have a minimal effect on other PDGFRα+ cell populations
To confirm that OPCs are the only cell type to undergo recombination in the CNS of PdgfrαCreERT2 transgenic mice, adult Pdgfrα-CreERT2::Rosa26-yellow fluorescent protein (YFP) transgenic mice were treated with Tamoxifen, and perfusion fixed 7 days later (P57+7)
Summary
The platelet-derived growth factor receptor (PDGFR) was first identified in 1982, as a protein expressed by fibroblasts and arterial smooth muscle cells [1]. In 1988 it was discovered that PDGFR was two receptors, named PDGFRα and PDGFRβ, that bind dimers of the PDGFs with different affinities [11]. PDGFRα is capable of binding all PDGFs except PDGF-DD [11,12], but has a strong affinity for the PDGF-A homodimer [13]. In the central nervous system (CNS), PDGFRα is selectively expressed by oligodendrocyte progenitor cells (OPCs) [14], and its activation by PDGF-AA has been shown to PLOS ONE | DOI:10.1371/journal.pone.0162858. In the central nervous system (CNS), PDGFRα is selectively expressed by oligodendrocyte progenitor cells (OPCs) [14], and its activation by PDGF-AA has been shown to PLOS ONE | DOI:10.1371/journal.pone.0162858 September 14, 2016
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