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Osterix-Cre transgene causes craniofacial bone development defect
Li Wang1, Yuji Mishina, Fei Liu
1Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
Calcified Tissue International
|January 1, 2015
Summary
Osteoblast-specific Cre expression in Osx-Cre mice causes severe craniofacial hypomineralization, particularly in sutures. This highlights the critical need for appropriate controls in gene knockout studies.
Area of Science:
- Developmental biology
- Genetics
- Craniofacial development
Background:
- The Cre/loxP system is essential for generating tissue-specific gene knockout mice.
- The inducible Osteoblast-specific transcription factor GFP::Cre (Osx-Cre) mouse line is widely used in bone research.
Purpose of the Study:
- To investigate the impact of Osx-Cre on craniofacial bone development.
- To evaluate the role of Cre expression in observed phenotypes.
Main Methods:
- Utilized inducible (Tet-off) Osx-GFP::Cre (Osx-Cre) mice.
- Analyzed craniofacial bone mineralization in newborn and mature mice.
- Administered Doxycycline to assess the effect of Cre expression inhibition.
- Isolated and cultured primary calvarial osteoblasts.
Main Results:
- Newborn Osx-Cre mice exhibited severe hypomineralization in parietal, frontal, nasal bones, and coronal sutures.
- Hypomineralization improved with age, but sutural defects persisted.
- Doxycycline treatment prevented cranial bone defects at birth.
- Primary calvarial osteoblasts from Osx-Cre mice showed normal differentiation capacity.
Conclusions:
- Cre expression in osteoblasts significantly impacts craniofacial bone development and mineralization.
- Sutural hypomineralization is a persistent defect in Osx-Cre mice.
- Cre-positive littermates are crucial controls for conditional gene deletion studies.
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