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doi: 10.1242/10.1242/dev.00491
DEVELOPMENT AND DISEASE |
1 Department of Molecular Biology and Pharmacology, Washington University
Medical School, Campus Box 8103, 660 S. Euclid Avenue, St. Louis, Missouri
63110, USA
2 Department of Molecular Biology, UT Southwestern Medical Center at Dallas,
5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
3 Department of Internal Medicine, Washington University Medical School, Campus
Box 8103, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA
* Author for correspondence (e-mail: dornitz{at}pcg.wustl.edu)
Accepted 3 March 2003
Human craniosynostosis syndromes, resulting from activating or neomorphic mutations in fibroblast growth factor receptor 2 (FGFR2), underscore an essential role for FGFR2 signaling in skeletal development. Embryos harboring homozygous null mutations in FGFR2 die prior to skeletogenesis. To address the role of FGFR2 in normal bone development, a conditional gene deletion approach was adopted. Homologous introduction of cre recombinase into the Dermo1 (Twist2) gene locus resulted in robust expression of CRE in mesenchymal condensations giving rise to both osteoblast and chondrocyte lineages. Inactivation of a floxed Fgfr2 allele with Dermo1-cre resulted in mice with skeletal dwarfism and decreased bone density. Although differentiation of the osteoblast lineage was not disturbed, the proliferation of osteoprogenitors and the anabolic function of mature osteoblasts were severely affected.
Key words: Fibroblast growth factor, FGF, FGF receptor, FGFR2, Endochondral bone growth, Chondrocyte, Osteoblast, Ossification, Dermo1, Twist2, Cre recombinase, Conditional gene deletion
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