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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
PubMed

Insights

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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