title: A quantitative method for defining high-arched palate using the Tcof1(+/-) mutant mouse as a model.
abstract: 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.
authors.affiliation: The Stowers Institute for Medical Research, Kansas City, MO, United States.
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Conley
authors.affiliation: The Stowers Institute for Medical Research, Kansas City, MO, United States.
authors.forename: Molly
authors.initials: M
authors.lastname: Hague
authors.affiliation: The Stowers Institute for Medical Research, Kansas City, MO, United States; Osaka University, Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurosaka
authors.affiliation: Manchester Academic Health Sciences Centre, Faculty of Medical and Human Sciences, Manchester, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Dixon
authors.affiliation: Manchester Academic Health Sciences Centre, Faculty of Medical and Human Sciences, Manchester, UK; University of Manchester, Faculty of Life Sciences, Manchester, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dixon
authors.affiliation: The Stowers Institute for Medical Research, Kansas City, MO, United States; Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, United States. Electronic address: pat@stowers.org.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Trainor
mesh_terms: D000818:Animals; D002972:Cleft Palate / Q000000981:diagnostic imaging / Q000196:embryology / Q000235:genetics; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D055786:Gene Knockout Techniques; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D021621:Imaging, Three-Dimensional; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000000981:diagnostic imaging / Q000196:embryology / Q000235:genetics; D008445:Maxillofacial Development / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018613:Microscopy, Confocal; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D010159:Palate / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000196:embryology; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology; D013045:Species Specificity
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C491352:Tcof1 protein, mouse
keywords: Cleft palate; High-arched palate; Mouse model; Palatogenesis; Quantitative imaging; Tcof1; Treacher Collins syndrome