1977/01/01 by Till Seime, Mille Kolind, Kathy Mikulec +6
Biochemistry, Genetics and Molecular Biology · Medicine · #Bone fractures and treatments #Cytokine Signaling Pathways and Interactions #Osteoarthritis Treatment and Mechanisms #Pluripotent Stem Cells Research #Tendon Structure and Treatment #Virus-based gene therapy research
paper · pdf · doi:10.1111/dgd.12184
openalex publication_date 1977/01/01 · crossref issued 2014/11/11 · crossref published 2014/11/11 · crossref published-online 2014/11/11 · crossref created 2014/11/11 · crossref published-print 2015/01/01 · crossref deposited 2022/04/21 · openalex created_date 2025/10/10 · crossref indexed 2026/07/28 · openalex updated_date 2026/08/01
Mouse models incorporating inducible Cre-ERT2/LoxP recombination coupled with sensitive fluorescent reporter lines are being increasingly used to track cell lineages in vivo. In this study we use two inducible reporter strains, Ai9iCol2a1 (Ai9×Col2a1-creERT2) to track contribution of chondrogenic progenitors during bone regeneration in a closed fracture model and Ai9i UBC (Ai9×UBC-creERT2) to examine methods for inducing localized recombination. By comparing with Ai9 littermate controls as well as inducible reporter mice not dosed with tamoxifen, we revealed significant leakiness of the CreERT2 system, particularly in the bone marrow of both lines. These studies highlight the challenges associated with highly sensitive reporters that may be activated without induction in tissues where the CreERT2 fusion is expressed. Examination of the growth plate in the Ai9iCol2a1 strain showed cells of the osteochondral lineage (cell co-staining with chondrocyte and osteoblast markers) labeled with the tdTom reporter. However, no such labeling was noted in healing fractures of Ai9iCol2a1 mice. Attempts to label a single limb using intramuscular injection of 4-hydroxytamoxifen in the Ai9i UBC strain resulted in complete labeling of the entire animal, comparable to intraperitoneal injection. While a challenge to interpret, these data are nonetheless informative regarding the limitations of these inducible reporter models, and justify caution and expansive controls in future studies using such models.