title: Rescue of the murine amelogenin null phenotype with two amelogenin transgenes.
abstract: The amelogenin proteins are required for normal enamel development, and the most abundant amelogenins expressed from alternatively spliced mRNAs are M180 and leucine-rich amelogenin protein (LRAP). The X-Chromosomal Amelogenin (Amelx) null [knockout (KO)] mouse has an enamel defect similar to human X-linked amelogenesis imperfecta. The disorganized enamel layer in KO mice is 10-20% of the thickness of wild-type (WT) enamel and lacks prismatic structures. When the KO mice were mated with mice that express the transgene M180-87, (TgM180-87) partial rescue of the phenotype was observed such that enamel thickness, volume, and density increased. A second transgene was introduced by mating TgM180 KO mice with TgLRAP mice, and male offspring were characterized for genotype and tooth phenotype was evaluated by scanning electron microscopy. The molar enamel thickness of TgM180-LRAP KO mice was further increased, and the structure was improved, with a more defined decussation pattern compared with singly rescued mice. We conclude that TgM180 provides significant rescue of the KO phenotype. Although the effectiveness of the LRAP transgene, alone, to rescue is less obvious, the addition of the LRAP transgene to the M180 transgene in KO enamel leads to an added improvement in both amount and structure and thus these transgenes function in a complementary manner. Together, the two most abundant amelogenins lead to the formation of obvious enamel decussation patterns.
authors.affiliation: Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA. cgibson@dental.upenn.edu
authors.forename: Carolyn W
authors.initials: CW
authors.lastname: Gibson
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Cynthia
authors.initials: C
authors.lastname: Suggs
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Kuehl
authors.forename: Megan K
authors.initials: MK
authors.lastname: Pugach
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: John T
authors.initials: JT
authors.lastname: Wright
mesh_terms: D017398:Alternative Splicing; D053523:Amelogenin / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D003743:Dental Enamel / Q000737:chemistry* / Q000648:ultrastructure*; D003744:Dental Enamel Hypoplasia / Q000235:genetics*; D003746:Dental Enamel Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D020033:Protein Isoforms; D019076:Transgenes; D055114:X-Ray Microtomography
chemical_list: D053523:Amelogenin; C507200:Amelx protein, mouse; D003746:Dental Enamel Proteins; D020033:Protein Isoforms; C067432:leucine-rich amelogenin peptide