Amelogenin-deficient mice display an amelogenesis imperfecta phenotype

Dental enamel is the hardest tissue in the body and cannot be replaced or r epaired, because the enamel secreting cells are lost at tooth eruption. X-l inked amelogenesis imperfecta (MIM 301200), a phenotypically diverse heredi tary 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 defi ned, these proteins constitute 90% of the enamel organic matrix. We have di srupted the amelogenin locus to generate amelogenin null mice, which displa y distinctly abnormal teeth as early as 2 weeks of age with chalky-white di scoloration. Microradiography revealed broken tips of incisors and molars a nd scanning electron microscopy analysis indicated disorganized hypoplastic enamel. The amelogenin null phenotype reveals that the amelogenins are app arently 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 ameloge nin proteins during enamel formation and for developing therapeutic approac hes for treating this developmental defect that affects the enamel.