ADAM10 Expression by Ameloblasts Is Essential for Proper Enamel Formation

ADAM10 is a multi-functional proteinase that can cleave approximately 100 different substrates. Previously, it was demonstrated that ADAM10 is expressed by ameloblasts, which are required for enamel formation. The goal of this study was to determine if ADAM10 is necessary for enamel development. Deletion of <i>Adam10</i> in mice is embryonically lethal and deletion of <i>Adam10</i> from epithelia is perinatally lethal. We therefore deleted <i>Adam10</i> from ameloblasts. Ameloblast-specific expression of the Tg(<i>Amelx</i>-i<i>Cre</i>)872pap construct was confirmed. These mice were crossed with <i>Adam10</i> floxed mice to generate <i>Amelx-</i>i<i>Cre</i>; <i>Adam10^fl/fl</i> mice (<i>Adam10</i> cKO). The <i>Adam10</i> cKO mice had discolored teeth with softer than normal enamel. Notably, the <i>Adam10</i> cKO enamel density and volume were significantly reduced in both incisors and molars. Moreover, the incisor enamel rod pattern became progressively more disorganized, moving from the DEJ to the outer enamel surface, and this disorganized rod structure created gaps and S-shaped rods. ADAM10 cleaves proteins essential for cell signaling and for enamel formation such as RELT and COL17A1. ADAM10 also cleaves cell-cell contacts such as E- and N-cadherins that may support ameloblast movement necessary for normal rod patterns. This study shows, for the first time, that ADAM10 expressed by ameloblasts is essential for proper enamel formation.