Mutations in the human
enamelin gene cause autosomal dominant hypoplastic
amelogenesis imperfecta in which the affected enamel is thin or absent. Study of
enamelin knockout NLS-lacZ knockin mice revealed that mineralization along the distal membrane of ameloblast is deficient, resulting in no true enamel formation. To determine the function of
enamelin during enamel formation, we characterized the developing teeth of the Enam-/- mice, generated
amelogenin-driven
enamelin transgenic mouse models, and then introduced
enamelin transgenes into the Enam-/- mice to rescue enamel defects. Mice at specific stages of development were subjected to morphologic and structural analysis using β-
galactosidase staining, immunohistochemistry, and transmission and scanning electron microscopy.
Enamelin expression was ameloblast-specific. In the absence of
enamelin, ameloblasts pathology became evident at the onset of the secretory stage. Although the aggregated ameloblasts generated matrix-containing
amelogenin, they were not able to create a well-defined enamel space or produce normal enamel crystals. When
enamelin is present at half of the normal quantity, enamel was thinner with enamel rods not as tightly arranged as in wild type suggesting that a specific quantity of
enamelin is critical for normal enamel formation.
Enamelin dosage effect was further demonstrated in transgenic mouse lines over expressing
enamelin. Introducing
enamelin transgene at various expression levels into the Enam-/- background did not fully recover enamel formation while a medium expresser in the Enam+/- background did. Too much or too little
enamelin abolishes the production of enamel crystals and prism structure.
Enamelin is essential for ameloblast integrity and enamel formation.