Enamel biomineralization defects result from alterations to amelogenin self-assembly

Enamel formation is a powerful model for the study of biomineralization. A key feature common to all biomineralizing systems is their dependency upon the biosynthesis of an extracellular organic matrix that is competent to di rect the formation of the subsequent mineral phase. The major organic compo nent of forming mouse enamel is the 180-amino-acid amelogenin protein (M180 ), whose ability to undergo self-assembly is believed to contribute to biom ineralization of vertebrate enamel. Two recently defined domains (A and B) within amelogenin appear essential for this self-assembly. The significance of these two domains has been demonstrated previously by the yeast two-hyb rid system, atomic force microscopy, and dynamic light scattering. Transgen ic animals were used to test the hypothesis that the self-assembly domains identified with in vitro model systems also operate in vivo. Transgenic ani mals bearing either a domain-A-deleted or domain-B-deleted amelogenin trans gene expressed the altered amelogenin exclusively in ameloblasts. This alte red amelogenin participates in the formation an organic enamel extracellula r matrix and, in turn, this matrix is defective in its ability to direct en amel mineralization. At the nanoscale level, the forming matrix adjacent to the secretory face of the ameloblast shows alteration in the size of the a melogenin nanospheres for either transgenic animal line. At the mesoscale l evel of enamel structural hierarchy, 6-week-old enamel exhibits defects in enamel rod organization due to perturbed organization of the precursor orga nic matrix. These studies reflect the critical dependency of amelogenin sel f-assembly in forming a competent enamel organic matrix and that alteration s to the matrix are reflected as defects in the structural organization of enamel. (C) 2000 academic Press.