title: Targeted overexpression of amelotin disrupts the microstructure of dental enamel.
abstract: We have previously identified amelotin (AMTN) as a novel protein expressed predominantly during the late stages of dental enamel formation, but its role during amelogenesis remains to be determined. In this study we generated transgenic mice that produce AMTN under the amelogenin (Amel) gene promoter to study the effect of AMTN overexpression on enamel formation in vivo. The specific overexpression of AMTN in secretory stage ameloblasts was confirmed by Western blot and immunohistochemistry. The gross histological appearance of ameloblasts or supporting cellular structures as well as the expression of the enamel proteins amelogenin (AMEL) and ameloblastin (AMBN) was not altered by AMTN overexpression, suggesting that protein production, processing and secretion occurred normally in transgenic mice. The expression of Odontogenic, Ameloblast-Associated (ODAM) was slightly increased in secretory stage ameloblasts of transgenic animals. The enamel in AMTN-overexpressing mice was much thinner and displayed a highly irregular surface structure compared to wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. Tomes' process, the hallmark of secretory stage ameloblasts, did not form in transgenic mice. Collectively our data demonstrate that the overexpression of amelotin has a profound effect on enamel structure by disrupting the formation of Tomes' process and the orderly growth of enamel prisms.
authors.affiliation: School of Dentistry, Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Lacruz
authors.forename: Yohei
authors.initials: Y
authors.lastname: Nakayama
authors.forename: James
authors.initials: J
authors.lastname: Holcroft
authors.forename: Van
authors.initials: V
authors.lastname: Nguyen
authors.forename: Eszter
authors.initials: E
authors.lastname: Somogyi-Ganss
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
authors.forename: Shane N
authors.initials: SN
authors.lastname: White
authors.forename: Michael L
authors.initials: ML
authors.lastname: Paine
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ganss
mesh_terms: D000565:Ameloblasts / Q000378:metabolism / Q000473:pathology; D053523:Amelogenin / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003743:Dental Enamel / Q000473:pathology / Q000648:ultrastructure*; D003746:Dental Enamel Proteins / Q000235:genetics / Q000378:metabolism*; D017886:Durapatite / Q000737:chemistry; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic
chemical_list: C490890:Ambn protein, mouse; D053523:Amelogenin; C507066:Amtn protein, mouse; D003746:Dental Enamel Proteins; D017886:Durapatite