title: Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development.
abstract: Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3-, and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by ∼20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length, and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. Anat Rec, 299:1110-1120, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts.|Department of Pediatric Dentistry and Orthodontics, College of Dentistry, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.
authors.forename: Mohammed K
authors.initials: MK
authors.lastname: Badri
authors.affiliation: Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ohyama
authors.affiliation: Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts.
authors.forename: Sundharamani
authors.initials: S
authors.lastname: Venkitapathi
authors.affiliation: Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan.|National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kamiya
authors.affiliation: Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Liège, 4000, Belgium.
authors.forename: Haruko
authors.initials: H
authors.lastname: Takeda
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
authors.forename: Manas
authors.initials: M
authors.lastname: Ray
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
authors.forename: Greg
authors.initials: G
authors.lastname: Scott
authors.affiliation: Graduate School of Environmental and Life Science, Okayama University, Okayama City, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Graduate School of Environmental and Life Science, Okayama University, Okayama City, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kunieda
authors.affiliation: Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan.|National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishina
authors.affiliation: Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mochida
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001846:Bone Development / Q000235:genetics*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D019465:Craniofacial Abnormalities / Q000378:metabolism / Q000473:pathology*; D004613:Ellis-Van Creveld Syndrome / Q000235:genetics / Q000473:pathology*; D005147:Facial Bones / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: C541939:EVC2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins
keywords: EVC2; Ellis-van Creveld syndrome; cephalometric analysis; craniofacial bone; knockout (KO) mouse