title: The leucine-rich amelogenin peptide alters the amelogenin null enamel phenotype.
abstract: BACKGROUND
  The amelogenin proteins secreted by ameloblasts during dental enamel development are required for normal enamel structure. Amelx null (KO) mice have hypoplastic, disorganized enamel similar to that of human patients with mutations in the AMELX gene, and provide a model system for studies of the enamel defect amelogenesis imperfecta. Because many amelogenin proteins are present in developing enamel due to RNA alternative splicing and proteolytic processing, understanding the function of individual amelogenins has been challenging.
  
  
  OBJECTIVE
  Our objective was to better understand the role of LRAP, a 59 amino acid leucine-rich amelogenin peptide, in the development of enamel.
  
  
  METHODS
  Teeth from transgenic mice that express LRAP under control of the Amelx regulatory regions were analyzed for mechanical properties, and transgenic males were mated with female KO mice. Male offspring with a null background that were transgene positive or transgene negative were compared to determine phenotypic differences using microcomputed tomography (microCT) and scanning electron microscopy (SEM).
  
  
  RESULTS
  Nanoindentation revealed no differences between LRAP transgenic and wild-type murine enamel. Using microCT, LRAPKO enamel volume and density measurements were similar to those from KO mice. However, in etched samples examined by SEM, the organization of the enamel rod pattern was altered by the presence of the LRAP transgene.
  
  
  CONCLUSIONS
  The presence of LRAP leads to changes in enamel appearance compared to enamel from KO mice. Expression of a combination of amelogenin transgenes in KO mice may lead to rescue of the individual characteristics of normal enamel.
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pa. 19104-6030, USA. gibson@biochem.dental.upenn.edu
authors.forename: Carolyn W
authors.initials: CW
authors.lastname: Gibson
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Bill
authors.initials: B
authors.lastname: Daly
authors.forename: Cynthia
authors.initials: C
authors.lastname: Suggs
authors.forename: Zhi-an
authors.initials: ZA
authors.lastname: Yuan
authors.forename: Hanson
authors.initials: H
authors.lastname: Fong
authors.forename: Darrin
authors.initials: D
authors.lastname: Simmons
authors.forename: Melissa
authors.initials: M
authors.lastname: Aragon
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Wright
mesh_terms: D053523:Amelogenin / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D003743:Dental Enamel / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D003746:Dental Enamel Proteins / Q000378:metabolism*; D003804:Dentin / Q000254:growth & development / Q000648:ultrastructure; D055119:Elastic Modulus; D005260:Female; D006244:Hardness; D007180:Incisor / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D036103:Nanotechnology; D009929:Organ Size; D010641:Phenotype; D014082:Tooth Fractures / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D053523:Amelogenin; D003746:Dental Enamel Proteins; C067432:leucine-rich amelogenin peptide