Evaluating Tissue-Specific Recombination in a Pdgfrα-CreERT2 Transgenic Mouse Line

PLoS One. 2016 Sep 14;11(9):e0162858. doi: 10.1371/journal.pone.0162858. eCollection 2016.

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.

MeSH terms

  • Animals
  • Cell Line
  • Cell Lineage / genetics
  • Female
  • Integrases / genetics
  • Integrases / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Oligodendroglia / metabolism*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Recombinant Proteins / metabolism
  • Recombination, Genetic*
  • Schwann Cells / metabolism
  • Sciatic Nerve / cytology
  • Stem Cells / metabolism*
  • Tamoxifen / pharmacology

Substances

  • Receptors, Estrogen
  • Recombinant Proteins
  • Tamoxifen
  • Receptor, Platelet-Derived Growth Factor alpha
  • Cre recombinase
  • Integrases

Grants and funding

We thank our colleagues at the University of Tasmania for their constructive feedback and suggestions for improvement. This research was supported by the National Health and Medical Research Council (grant numbers 1045240 and 1066025) and Multiple Sclerosis Research Australia (15-054). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.