74 Craniofacial Anomalies Associated with Wnt5a and Ror2 Mutations

Thursday, March 22, 2012: 8 a.m. - 9:30 a.m.
Presentation Type: Oral Session
S. BEIRAGHI1, V. LEON-SALAZAR2, A.S. FOK1, Y. YINGZI3, M.L. CUNNINGHAM4, and M. MAGA5, 1University of Minnesota, Minneapolis, MN, 2Orthodontics, University of Minnesota, Minneapolis, MN, 3National Human Genome Research Institute, Bethesda, MD, 4Seattle Children's Hospital, Seattle, WA, 5Department of Pediatrics, University of Washington, Seattle, WA

Mutation of the ROR2 and WNT5A genes in humans cause Robinow syndrome (RS)  which is characterized by craniofacial anomalies including prominent forehead, marked hypertelorism, short nose, mandibular hypoplasia, and upturned nostril, among others. Animal studies have also shown that these phenotypical characteristics are also manifested in Ror2-/- and Wnta5-/- newborn mice. The aim of this study was to perform a three-dimensional analysis of the skeletal and dental characteristics of ror2 and wnt5a mutant mice using micro computed tomography (μCT ).  


Eight E18.5 mouse heads (two Wnt5a-/-,  and two Ror2-/-, two wild-type controls for each mutant) were used in this study. High-resolution μCT of each head was obtained using  a  X-Tek XTV μCT scanner (Nikon metrology NV, Leuven, Belgium) at  90 kV, 91 μA, and 2000 projections. Images were reconstructed using CT PRO 2.2 and saved as DICOM files for further three-dimensional morphometric analysis. Qualitative and quantitative comparisons included: Craniofacial bone volume, maxillary and mandibular size and shape variation, trabecular bone pattern, and tooth development.


The preliminary result of this study showed that both Wnt5a-/- and Ror2-/- mice had a significant reduction in the facial and cranial vault development when compared to the wild-type mice. Bone volume, maxillary and mandibular lengths, and the trabecular bone pattern were reduced in both mutants mice. Interestingly, the mandible, maxilla, and teeth in the wnt5a-/- mice were more severely affected than in the Ror2-/-.


Our preliminary data confirms that mutation of the Wnt5a/Ror2 pathway affects skeletal and dental growth and development and causes severe malformation of the maxilla and mandible alveolar bone.

Keywords: Animal, Gene expression, Genetics, Growth & development and Robinow Syndrome