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Frontonasal process-specific disruption of AP-2α results in postnatal midfacial hypoplasia, vascular anomalies, and nasal cavity defects

Developmental Biology
Publication Date
DOI: 10.1016/j.ydbio.2003.10.033
  • Ap-2
  • Craniofacial
  • Intramembranous Ossification
  • Suture
  • Frontonasal
  • Differentiation
  • Mouse
  • Midfacial Hypoplasia
  • Cre Recombinase
  • Interfrontal Bone


Abstract A majority of the bones of the vertebrate cranial vault and craniofacial complex develop via intramembranous ossification, and are separated by fibrous sutures that undergo osteogenic differentiation in response to growth stimuli. Craniosynostosis is a common human birth defect that results from the premature bony fusion within skull sutures, and causes a myriad of complications including mental retardation and craniofacial anomalies. Synostosis of facial sutures has been reported to cause midfacial hypoplasia in some craniosynostosis cases, but most studies focus on cranial vault sutures. In this study, we have generated a mouse model of frontonasal suture synostosis and midfacial hypoplasia through the tissue-specific elimination of the AP-2α transcription factor. We report here the generation AP-2CRE, a frontonasal process (FNP)- and limb-specific CRE recombinase allele that is directed by human AP-2α promoter and enhancer elements. We used the AP-2CRE line in combination with the conditional AP-2α line to produce a new frontonasal knockout (FKO) mutant that lacks AP-2α in the FNP and limbs. FKO mice exhibit shortened snouts and wide-set eyes that become apparent at postnatal day 15. The most prominent defects in FKO snouts are (1) a lack of growth within the frontonasal sutures, and (2) a reduction in the snout vasculature. Additional defects are observed in the FKO nasal bones and sutures, the nasal cavity cartilage and bony projections, and the olfactory epithelium. The characteristics of the FKO mouse model are a unique combination of midfacial growth anomalies, and provide the first evidence that AP-2α is essential for appropriate postnatal craniofacial morphogenesis.

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