A quantitative method for defining high-arched palate using the Tcof1+/− mutant mouse as a model

• Published in: Developmental biology 2016-07, Vol.415 (2), p.296-305
• Main Authors: Conley, Zachary R., Hague, Molly, Kurosaka, Hiroshi, Dixon, Jill, Dixon, Michael J., Trainor, Paul A.
• Format: Article
• Language: English
• Subjects: animal models; Animals; Cleft palate; Cleft Palate - diagnostic imaging; Cleft Palate - embryology; Cleft Palate - genetics; Crosses, Genetic; Disease Models, Animal; embryogenesis; Female; Gene Knockout Techniques; Genes, p53; Heterozygote; High-arched palate; Humans; Imaging, Three-Dimensional; Male; Mandibulofacial Dysostosis - diagnostic imaging; Mandibulofacial Dysostosis - embryology; Mandibulofacial Dysostosis - genetics; Maxillofacial Development - genetics; Maxillofacial Development - physiology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Microscopy, Confocal; Mouse model; mutants; nasal cavity; Nuclear Proteins - genetics; Nuclear Proteins - physiology; palate; Palate - abnormalities; Palate - diagnostic imaging; Palate - embryology; Palatogenesis; pathogenesis; Phenotype; Phosphoproteins - genetics; Phosphoproteins - physiology; pups; quantitative analysis; Quantitative imaging; Species Specificity; Tcof1; Treacher Collins syndrome
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2015.12.020

The palate functions as the roof of the mouth in mammals, separating the oral and nasal cavities. Its complex embryonic development and assembly poses unique susceptibilities to intrinsic and extrinsic disruptions. Such disruptions may cause failure of the developing palatal shelves to fuse along the midline resulting in a cleft. In other cases the palate may fuse at an arch, resulting in a vaulted oral cavity, termed high-arched palate. There are many models available for studying the pathogenesis of cleft palate but a relative paucity for high-arched palate. One condition exhibiting either cleft palate or high-arched palate is Treacher Collins syndrome, a congenital disorder characterized by numerous craniofacial anomalies. We quantitatively analyzed palatal perturbations in the Tcof1+/− mouse model of Treacher Collins syndrome, which phenocopies the condition in humans. We discovered that 46% of Tcof1+/− mutant embryos and new born pups exhibit either soft clefts or full clefts. In addition, 17% of Tcof1+/− mutants were found to exhibit high-arched palate, defined as two sigma above the corresponding wild-type population mean for height and angular based arch measurements. Furthermore, palatal shelf length and shelf width were decreased in all Tcof1+/− mutant embryos and pups compared to controls. Interestingly, these phenotypes were subsequently ameliorated through genetic inhibition of p53. The results of our study therefore provide a simple, reproducible and quantitative method for investigating models of high-arched palate. •Cleft palate is associated with functional and esthetic challenges.•High-arched palate is an example of perturbed palatogenesis.•High-arched palate is also known as pseudo cleft or vaulted palate.•There is a paucity of models for investigating high-arched palate.•We established a quantitative method for defining high-arched palate.