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Updated: Apr 5, 2026
Co-localization of Cell Lineage Markers and the Tomato Signal
Published on: December 28, 2016
Col2-Cre and tamoxifen-inducible Col2-CreER target different cell populations in the knee joint
M Nagao1, C W Cheong1, B R Olsen1
1Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Objective:
Collagen type 2 (Col2)-Cre or tamoxifen-inducible Col2-CreER transgenic mouse lines have been used for studies to explore the cellular and molecular pathogenesis of osteoarthritis (OA). The purpose of this study is to investigate whether the targeted cells are the same or different in the two mouse lines.
Methods:
We crossed tamoxifen inducible Col2-CreER and Col2-Cre mice with Rosa tdTomato reporter mice and analyzed the labeling patterns at different time points.
Results:
In the Col2-CreER mice, 90.8 [95% confidence interval (CI) (88.3, 93.2)] and 82.8 (77.4, 88.3) % of the articular surface cells are Tomato positive when tamoxifen was administered at 2 and 2.5 weeks of age and strong activity was observed even 4.5 months after injection. However, 46.0 (32.8, 59.1) and 22.2 (11.7, 32.6) % of the surface cells were Tomato positive when tamoxifen was administered at 3 and 4 weeks of age, respectively. Little to no Tomato activity in the articular surface cells was observed when tamoxifen was administered at 8 weeks of age. At any stage of tamoxifen injection, the Tomato activity was detected in growth plate and epiphyseal bone in addition to articular chondrocytes, but little in endosteum and not in the synovium and ligament. In contrast, the targeted tissues in the Col2-Cre mouse line were articular cartilage, growth plate, meniscus, endosteum, ligament, bone and synovium.
Conclusions:
This study demonstrates that the pattern of targeted cells in the inducible Col2-CreER mice are partially overlapping with but different from that of targeted cells in Col2-Cre mice and the pattern varies dependent on when tamoxifen is administered.
Insights
The inducible Col2-CreER mouse line targets articular chondrocytes, but cell labeling varies with tamoxifen timing. This differs from Col2-Cre mice, which target a broader range of joint tissues, including cartilage, bone, and synovium.
Area of Science:
- Biomedical research
- Genetics
- Osteoarthritis research
Background:
- Collagen type 2 (Col2)-Cre and Col2-CreER transgenic mouse lines are crucial tools for osteoarthritis (OA) research.
- Understanding the precise cell populations targeted by these lines is vital for accurate OA pathogenesis studies.
Purpose of the Study:
- To compare the cell targeting specificity of Col2-CreER and Col2-Cre mouse lines.
- To determine if these lines target the same or different cell populations in the context of OA research.
Main Methods:
- Utilized tamoxifen-inducible Col2-CreER and constitutive Col2-Cre mouse lines crossed with Rosa tdTomato reporter mice.
- Analyzed tdTomato labeling patterns in various tissues at different time points post-tamoxifen administration or constitutive expression.
Main Results:
- Col2-CreER mice showed tamoxifen-dependent labeling of articular chondrocytes, with patterns varying significantly based on administration age (e.g., 90.8% at 2 weeks vs. 22.2% at 4 weeks).
- Col2-CreER labeling was observed in articular cartilage, growth plate, and epiphyseal bone, but not synovium or ligament.
- Col2-Cre mice targeted a wider array of tissues, including articular cartilage, growth plate, meniscus, endosteum, ligament, bone, and synovium.
Conclusions:
- The cell targeting profiles of Col2-CreER and Col2-Cre mouse lines are distinct, with partial overlap.
- The temporal administration of tamoxifen critically influences the cell labeling pattern in Col2-CreER mice.
- These findings highlight the importance of careful consideration of mouse line choice and experimental timing in OA research.
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