Background: Dentin and enamel are clearly separated by a transitional zone referred to as the dentin-enamel junction (DEJ). This transition from dentin to enamel is a clearly definable zone with its own unique chemical and structural properties. Kallikrein-4 is a secreted serine protease found primarily in enamel and prostate. In enamel, kallikrein-4 is secreted from transition-stage ameloblast cells. In contrast amelogenin, the major enamel matrix protein, is secreted prior to kallikrein-4 from these same cells. Thus in ameloblasts, kallikrein-4 expression and activity is present after the formation of the enamel extracellular matrix, and also after the early enamel mineralization events. In vitro, it has been demonstrated that amelogenin is a substrate of kallikrein-4. Objectives: To observe the phenotype of enamel and DEJ in animals when kallikrein-4 and amelogenin are co-expressed during amelogenesis. Methods: and Results: Transgenic mice over-expressing kallikrein-4 in a spatiotemporal pattern mirroring that of the endogenous amelogenin show a disruption to the integrity of the DEJ, with enamel prismatic structures extending into dentin. The enamel of these transgenic mice also has vast regions that are both hypomineralized and hypoplastic. Conclusion: From these studies it is apparent that disruptions to the normal spatiotemporal expression of kallikrein-4 clearly impact on the enamel matrix, enamel mineralization and the integrity of the DEJ.

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