Generation of a BAC transgenic mouse strain that expresses CreERT and a fluorescent protein under the transcriptional control of the Fzd5 locus.

Background: The expression of FZD5 distinguishes immature human mesenchymal stem/stromal cells (MSC) in cultures, and the function of FZD5 is crucial for maintaining the proliferation and multilineage differentiation capacity of human MSC. We herein investigated whether Fzd5 expression also marks undifferentiated MSC in animals.

Methods: We generated a transgenic mouse strain (Fzd5-CreERT-tFP635) that expresses CreERT and the fluorescent protein, TurboFP635 (tFP635), under the transcriptional control of the Fzd5 gene using the BAC transgenic technique, and identified cells expressing tFP635 by flow cytometry. We also conducted lineage tracing with this strain.

Results: In the bone marrow of transgenic mice, tFP635 was preferentially expressed in MSC, Leptin receptor-expressing MSC (LepRMSCs), and some Pdgfrα Sca1 MSC (PαS). Inducible lineage tracing using the Fzd5-CreERT-tFP635; CAG-CAT-EGFP strain at the adult stage showed that Fzd5-expressing cells and their descendants labeled with GFP were progressively dominant in LepRMSC and PαS, and GFP cells persisted for 1 year after the activation of CreERT. Adipocyte progenitor cells (APCs), osteoblast progenitor cells (OPCs), and Cd51 stromal cells were also labeled with GFP.

Conclusions: Our transgenic mouse marks two different types of MSC, LepRMSC and PαS.