title: Enamelysin (matrix metalloproteinase 20)-deficient mice display an amelogenesis imperfecta phenotype.
abstract: Enamelysin is a tooth-specific matrix metalloproteinase that is expressed during the early through middle stages of enamel development. The enamel matrix proteins amelogenin, ameloblastin, and enamelin are also expressed during this same approximate developmental time period, suggesting that enamelysin may play a role in their hydrolysis. In support of this interpretation, recombinant enamelysin was previously demonstrated to cleave recombinant amelogenin at virtually all of the precise sites known to occur in vivo. Thus, enamelysin is likely an important amelogenin-processing enzyme. To characterize the in vivo biological role of enamelysin during tooth development, we generated an enamelysin-deficient mouse by gene targeting. Although mice heterozygous for the mutation have no apparent phenotype, the enamelysin null mouse has a severe and profound tooth phenotype. Specifically, the null mouse does not process amelogenin properly, possesses an altered enamel matrix and rod pattern, has hypoplastic enamel that delaminates from the dentin, and has a deteriorating enamel organ morphology as development progresses. Our findings demonstrate that enamelysin activity is essential for proper enamel development.
authors.affiliation: Matrix Metalloproteinase Unit, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Caterina
authors.forename: Ziedonis
authors.initials: Z
authors.lastname: Skobe
authors.forename: Joanne
authors.initials: J
authors.lastname: Shi
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ding
authors.forename: James P
authors.initials: JP
authors.lastname: Simmer
authors.forename: Henning
authors.initials: H
authors.lastname: Birkedal-Hansen
authors.forename: John D
authors.initials: JD
authors.lastname: Bartlett
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D053523:Amelogenin; D000818:Animals; D003746:Dental Enamel Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D005822:Genetic Vectors; D005838:Genotype; D006579:Heterozygote; D007438:Introns; D053519:Matrix Metalloproteinase 20; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D008957:Models, Genetic; D008963:Molar / Q000502:physiology / Q000648:ultrastructure; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D012313:RNA / Q000378:metabolism
chemical_list: D053523:Amelogenin; C507200:Amelx protein, mouse; D003746:Dental Enamel Proteins; D010455:Peptides; D012313:RNA; D053519:Matrix Metalloproteinase 20; D020782:Matrix Metalloproteinases; C507113:Mmp20 protein, mouse