title: Amelogenin-deficient mice display an amelogenesis imperfecta phenotype.
abstract: Dental enamel is the hardest tissue in the body and cannot be replaced or repaired, because the enamel secreting cells are lost at tooth eruption. X-linked amelogenesis imperfecta (MIM 301200), a phenotypically diverse hereditary disorder affecting enamel development, is caused by deletions or point mutations in the human X-chromosomal amelogenin gene. Although the precise functions of the amelogenin proteins in enamel formation are not well defined, these proteins constitute 90% of the enamel organic matrix. We have disrupted the amelogenin locus to generate amelogenin null mice, which display distinctly abnormal teeth as early as 2 weeks of age with chalky-white discoloration. Microradiography revealed broken tips of incisors and molars and scanning electron microscopy analysis indicated disorganized hypoplastic enamel. The amelogenin null phenotype reveals that the amelogenins are apparently not required for initiation of mineral crystal formation but rather for the organization of crystal pattern and regulation of enamel thickness. These null mice will be useful for understanding the functions of amelogenin proteins during enamel formation and for developing therapeutic approaches for treating this developmental defect that affects the enamel.
authors.affiliation: Department of Anatomy and Histology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania 19104, USA. gibson@biochem.dental.upenn.edu
authors.forename: C W
authors.initials: CW
authors.lastname: Gibson
authors.forename: Z A
authors.initials: ZA
authors.lastname: Yuan
authors.forename: B
authors.initials: B
authors.lastname: Hall
authors.forename: G
authors.initials: G
authors.lastname: Longenecker
authors.forename: E
authors.initials: E
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Thyagarajan
authors.forename: T
authors.initials: T
authors.lastname: Sreenath
authors.forename: J T
authors.initials: JT
authors.lastname: Wright
authors.forename: S
authors.initials: S
authors.lastname: Decker
authors.forename: R
authors.initials: R
authors.lastname: Piddington
authors.forename: G
authors.initials: G
authors.lastname: Harrison
authors.forename: A B
authors.initials: AB
authors.lastname: Kulkarni
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D053523:Amelogenin; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D017931:DNA Primers; D003746:Dental Enamel Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014070:Tooth / Q000648:ultrastructure
chemical_list: D053523:Amelogenin; C507200:Amelx protein, mouse; D017931:DNA Primers; D003746:Dental Enamel Proteins