title: Enamel and dental anomalies in latent-transforming growth factor beta-binding protein 3 mutant mice.
abstract: Latent-transforming growth factor beta-binding protein 3 (LTBP-3) is important for craniofacial morphogenesis and hard tissue mineralization, as it is essential for activation of transforming growth factor-β (TGF-β). To investigate the role of LTBP-3 in tooth formation we performed micro-computed tomography (micro-CT), histology, and scanning electron microscopy analyses of adult Ltbp3-/- mice. The Ltbp3-/- mutants presented with unique craniofacial malformations and reductions in enamel formation that began at the matrix formation stage. Organization of maturation-stage ameloblasts was severely disrupted. The lateral side of the incisor was affected most. Reduced enamel mineralization, modification of the enamel prism pattern, and enamel nodules were observed throughout the incisors, as revealed by scanning electron microscopy. Molar roots had internal irregular bulbous-like formations. The cementum thickness was reduced, and microscopic dentinal tubules showed minor nanostructural changes. Thus, LTBP-3 is required for ameloblast differentiation and for the formation of decussating enamel prisms, to prevent enamel nodule formation, and for proper root morphogenesis. Also, and consistent with the role of TGF-β signaling during mineralization, almost all craniofacial bone components were affected in Ltbp3-/- mice, especially those involving the upper jaw and snout. This mouse model demonstrates phenotypic overlap with Verloes Bourguignon syndrome, also caused by mutation of LTBP3, which is hallmarked by craniofacial anomalies and amelogenesis imperfecta phenotypes.
authors.affiliation: Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.|CNRS UMR_7104, INSERM U964, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre Européen de Recherche en Biologie et en Médecine (CERBM), Université de Strasbourg, Illkirch, France.|Faculty of Dentistry, Pediatric Dentistry, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Supawich
authors.initials: S
authors.lastname: Morkmued
authors.affiliation: Biomaterials and Bioengineering, Inserm UMR1121 Strasbourg, Université de Strasbourg, Strasbourg, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hemmerle
authors.affiliation: Biomaterials and Bioengineering, Inserm UMR1121 Strasbourg, Université de Strasbourg, Strasbourg, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Mathieu
authors.affiliation: CNRS UMR_7104, INSERM U964, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre Européen de Recherche en Biologie et en Médecine (CERBM), Université de Strasbourg, Illkirch, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Laugel-Haushalter
authors.affiliation: Department of Cell Biology, New York University Medical Center, New York, NY, USA.
authors.forename: Branka
authors.initials: B
authors.lastname: Dabovic
authors.affiliation: Department of Cell Biology, New York University Medical Center, New York, NY, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Rifkin
authors.affiliation: CNRS UMR_7104, INSERM U964, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre Européen de Recherche en Biologie et en Médecine (CERBM), Université de Strasbourg, Illkirch, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Dollé
authors.affiliation: Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.|CNRS UMR_7104, INSERM U964, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre Européen de Recherche en Biologie et en Médecine (CERBM), Université de Strasbourg, Illkirch, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Niederreither
authors.affiliation: Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.|CNRS UMR_7104, INSERM U964, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre Européen de Recherche en Biologie et en Médecine (CERBM), Université de Strasbourg, Illkirch, France.|Pôle de Médecine et Chirurgie Bucco-Dentaires, Centre de Référence des Manifestations Odontologiques des Maladies Rares, O Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Bloch-Zupan
mesh_terms: D000565:Ameloblasts / Q000378:metabolism; D000566:Amelogenesis / Q000235:genetics*; D000567:Amelogenesis Imperfecta / Q000235:genetics; D000818:Animals; D003743:Dental Enamel / Q000002:abnormalities* / Q000648:ultrastructure; D005838:Genotype; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics; D010641:Phenotype; D014074:Tooth Calcification / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D055114:X-Ray Microtomography
chemical_list: D053779:Latent TGF-beta Binding Proteins; C509039:Ltbp3 protein, mouse; D016212:Transforming Growth Factor beta
keywords: Ltbp3; amelogenesis; enamel; mouse; scanning electron microscopy