DRAGON, a member of the family of repulsive guidance molecules (RGMs), is the first bone morphogenetic protein (BMP) co-receptor to - be identified. DRAGON facilitates binding of BMP ligands to signaling receptors and enhances BMP signaling. Complex and precise regulation of BMP signaling is required to ensure normal dental and craniofacial development. Objective: The purpose of this study is to examine the dental and craniofacial phenotype of DRAGON knockout mice. Methods: DRAGON knockout mice were generated at the Biozentrum, Switzerland, and maintained at the animal facility in Mass. General Hospital. Heterozygote mice were bred to produce mice that were homozygous for the null mutation. Faxitron X-Ray radiography and histology were used to analyze the craniofacial complex of newborn (P0) and two-week old (P14) knockout mice and their wild-type littermate controls. Results: DRAGON knockout mice die at 17days. At P0 they exhibit narrow maxilla and mandible and small size of the craniofacial complex. At P14, they exhibit abnormal craniofacial development, brittle and translucent incisors and unerupted maxillary and mandibular molar teeth. Radiographic and histologic analysis of the mandibular dentoalveolar complex of knockout mice demonstrates severely diminished dentin formation in the incisor and molars of both maxilla and mandible. In the knockout animals, molar root development initiates but fails to progress. Conclusions: We provide the first in vivo evidence that in DRAGON knockout mice, reduced levels of BMP signaling lead to delayed tooth eruption, dental and craniofacial defects. Future studies will aim to elucidate the specific mechanisms involved.

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