Abstract
Dental enamel is the hardest tissue in the body and cannot be replaced or repaired, because the enamel secreting cells are lost at tooth eruption. X-linked amelogenesis imperfecta (MIM 301200), a phenotypically diverse hereditary disorder affecting enamel development, is caused by deletions or point mutations in the human X-chromosomal amelogenin gene. Although the precise functions of the amelogenin proteins in enamel formation are not well defined, these proteins constitute 90% of the enamel organic matrix. We have disrupted the amelogenin locus to generate amelogenin null mice, which display distinctly abnormal teeth as early as 2 weeks of age with chalky-white discoloration. Microradiography revealed broken tips of incisors and molars and scanning electron microscopy analysis indicated disorganized hypoplastic enamel. The amelogenin null phenotype reveals that the amelogenins are apparently not required for initiation of mineral crystal formation but rather for the organization of crystal pattern and regulation of enamel thickness. These null mice will be useful for understanding the functions of amelogenin proteins during enamel formation and for developing therapeutic approaches for treating this developmental defect that affects the enamel.
Highlights
Dental enamel, the hard tissue that covers the crown of the tooth, is the most highly mineralized tissue in the body
Amelogenin proteins constitute 90% of the extracellular matrix secreted by ameloblasts, and these proteins are cleaved in a regulated process during enamel maturation [1, 2]
X-linked amelogenesis imperfecta (AI)1 is an inherited enamel defect characterized by phenotypic variability in which patients present with hypoplastic defects and/or hypomineralization where the enamel mineral content is decreased
Summary
The amelogenin null phenotype reveals that the amelogenins are apparently not required for initiation of mineral crystal formation but rather for the organization of crystal pattern and regulation of enamel thickness. These null mice will be useful for understanding the functions of amelogenin proteins during enamel formation and for developing therapeutic approaches for treating this developmental defect that affects the enamel. The marked phenotypic variability resulting from different AMELX mutations suggests that various amelogenin proteins or protein domains have different functions during enamel development This finding is consistent with the observation of extensive alternative splicing of the amelogenin primary transcript, even though the gene is active only in teeth [11,12,13,14]. The hypoplastic enamel layer in the null mice illustrates the importance of amelogenins to generate correct enamel thickness, a second proposed function for amelogenin proteins
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