Craniomaxillofacial morphology in a murine model of ephrinB1 conditional deletion in osteoprogenitor cells. (May 2022)

• Record Type: Journal Article
• Authors: Bereza, Samuel; Yong, Robin; Gronthos, Stan; Arthur, Agnieszka; Ranjitkar, Sarbin; Anderson, Peter J.
• Is Part Of: Archives of oral biology. Volume 137(2022)
• Publication Date: 2022-05
• Subjects: CFND Craniofrontonasal dysplasia -- Cre Cyclisation recombination enzyme (a site-specific DNA recombinase) -- Osx Osterix (master regulator of bone formation) -- EfnB1OB-/- conditional deletion of EfnB1 by Cre under the control of the Osx promoter -- Osx:Cre tTA:Osx1-GFP:Cre control mice (in which Cre is activated under the control of the Osterix promoter without deleting EfnB1 because the gene has not been flanked by lox P sites); Craniofacial -- Maxillofacial -- EFNB1 mutation -- Craniofrontonasal dysplasia -- Phenomics; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2022.105389
• Languages: English
• ISSNs: 0003-9969

Abstract

Abstract: Objective: EFNB1 mutation causes craniofrontonasal dysplasia (CFND), a congenital syndrome associated with craniomaxillofacial anomalies characterised by coronal craniosynostosis, orbital hypertelorism, and midface dysplasia. The aim of this murine study was to investigate the effect of the EfnB1 conditional gene deletion in osteoprogenitor cells on the craniomaxillofacial skeletal morphology. Design: The skulls of male and female mice, in which EfnB1 was deleted by Cre (a site-specific DNA recombinase) under the control of the Osterix ( Osx ) promoter ( EfnB1 OB -/- ), were compared to those without EfnB1 deletion ( Osx:Cre control) at two ages (4 and 8 weeks; n = 6 per group). The three-dimensional micro-computed tomography reconstructions were prepared to calculate 17 linear measurements in the cranial vault (brain box), midface and mandible. Coronal and sagittal sutures from the 8-week-old mice were also subjected to histological examination. Results: EfnB1 OB -/- mice displayed significantly larger cranial height, larger interorbital and nasal widths, smaller maxillary width than controls by 8 weeks ( p < 0.05), but mandibular size was not significantly different ( p > 0.05). Binomial testing showed significantly smaller EfnB1 OB -/- skulls at 4 weeks but larger at 8 weeks ( p < 0.05). Histological examination revealed increased bony fusion and fibrous connective tissue deposition at the coronal suture of EfnB1 OB -/- mice compared with controls. Conclusions: Craniofacial phenotype of the murine model of EfnB1 deletion in osteoprogenitor cells partially represents the human CFND phenotype, with implications for better understanding mechanisms involved in skeletal morphogenesis and malocclusion. Highlights: EfnB1 deletion in mice ( EfnB1 OB -/- ) displays cranial and midfacial dysplasia. The coronal suture of EfnB1 OB -/- mice show early signs of craniosynostosis. EfnB1 OB -/- mice partially represent phenotypes of human craniofrontonasal dysplasia. Cleft palate does not occur in EfnB1 OB -/- mice.