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. Author manuscript; available in PMC: 2020 Nov 28.
Published in final edited form as: Nat Rev Mol Cell Biol. 2020 Sep 8;21(11):696–711. doi: 10.1038/s41580-020-00279-w

Table 1 |.

Cre models applied for osteoblast lineage studies

Cre model Targeted cells Advantages Disadvantages Refs
Sox9 SSCs, osteochondroprogenitor cells Overcomes embryonic lethality of Sox9 heterozygous mutant mice; expressed throughout the lifetime of mice from the neonatal stage to old age Potential for off-target Cre-mediated recombination in intestines and pancreas 203
Grem1 Osteochondroprogenitor cells, bone stromal cells Expression of cells concentrated in metaphysis; distinct from mesenchymal stem cells Potential for off-target Cre-mediated recombination in intestines; low level of fibroblast CFUs (~1%) in in vitro studies forself-renewal 36
Osx SSCs, osteoblast progenitor cells Expression is specific to osteoblasts; expression is associated with invading blood vessels during development Unable to study precursor cells that have not committed to the osteoblast lineage fate 204
Prrxl SSCs Expressed throughout the lifetime of mice from the neonatal stage to old age; presence of self-renewal properties for bulk cell culture in vitro Potential off-target effects around the eye 205
Sost Mature osteocytes Used a Sost gene within a BAC clone for better expression; no off-target effects present in osteoblasts or myocytes Potential off-target effects in haematopoietic cells and osteoclasts 206
Pthrp (also known as Pthih) SSCs, osteochondroprogenitor cells, bone stromal cells Stromal contribution; expressed throughout the lifetime of mice from the neonatal stage to old age Involved in long-term maintenance of skeletal integrity; predilection for chondrogenesis over osteogenesis 42
Runx2 Mature osteoblasts Can be used to determine gene function in mature osteoblasts; robust expression and recombination Reporter leakage into cartilage cells 204
Ctsk SSCs in the periosteum Can be used to determine the function of SSCs found in the periosteum Potential deletion of gene in germline cells 43
Hoxa11 SSCs in the periosteum Labelling of cells from development until adulthood allows cell lineage tracing Hox11+ SSCs only mark a subset of the entire SSC population 26,28,207

BAC, bacterial artificial chromosome; CFU, colony-forming unit; Cre, Cre recombinase; SSC, skeletal stem cell.