title: Abnormal enamel development in a cystic fibrosis transgenic mouse model.
abstract: Cystic fibrosis (CF) is a hereditary condition that affects cAMP-regulated chloride channels in epithelial tissues due to a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recently, a transgenic CF mouse model was developed at UNC that exhibits no CFTR expression. Interestingly, the CF mouse demonstrates abnormal incisor enamel. Therefore, the purpose of this investigation was to characterize the enamel in this CF mouse model. Incisors from CF and normal mice were evaluated by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The enamel proteins were examined by amino acid analysis, SDS-PAGE, and Western blot. Gross examination showed that 100% of CF mice had soft, chalky white incisor enamel, while the enamel of normal mice was hard and yellow-brown. LM indicated that the ameloblasts in the CF mice underwent premature degeneration shortly after completion of the secretory phase. The CF mouse enamel appeared to be of relatively normal thickness and showed a prism structure similar to that of normal mouse enamel. However, the CF mouse enamel crystallites appeared to have a rough granular surface compared with normal enamel. SDS-PAGE indicated that mature CF enamel retained low-molecular-weight material (approximately 20 kDa), whereas normal mature enamel did not. This low-molecular-weight material cross-reacted with anti-amelogenin antibodies in Western blot analysis. This investigation shows that abnormal CFTR expression in the mouse results in developmental abnormalities in the incisor enamel. Although further investigation is required to determine the mechanism leading to abnormal enamel formation, the CF mouse provides a potentially useful animal model for investigating aberrant enamel development.
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry, University of North Carolina at Chapel Hill 27599-7450, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Wright
authors.forename: C L
authors.initials: CL
authors.lastname: Kiefer
authors.forename: K I
authors.initials: KI
authors.lastname: Hall
authors.forename: B R
authors.initials: BR
authors.lastname: Grubb
mesh_terms: D000566:Amelogenesis; D053523:Amelogenin; D000818:Animals; D003460:Crystallization; D003550:Cystic Fibrosis / Q000235:genetics / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D003743:Dental Enamel / Q000473:pathology* / Q000648:ultrastructure; D003746:Dental Enamel Proteins / Q000032:analysis; D004195:Disease Models, Animal; D006579:Heterozygote; D006720:Homozygote; D007180:Incisor; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning
chemical_list: D053523:Amelogenin; C507200:Amelx protein, mouse; D003746:Dental Enamel Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator