Odontogenesis-associated phosphoprotein truncation blocks ameloblast transition into maturation in Odaph(C41*/C41*) mice

Mutations of Odontogenesis-Associated Phosphoprotein (ODAPH, OMIM *614829) cause autosomal recessive amelogenesis imperfecta, however, the function of ODAPH during amelogenesis is unknown. Here we characterized normal Odaph expression by in situ hybridization, generated Odaph truncation mice using CRISPR/Cas9 to replace the TGC codon encoding Cys41 into a TGA translation termination codon, and characterized and compared molar and incisor tooth formation in Odaph(+/+), Odaph(+/C41*), and Odaph(C41*/C41*) mice. We also searched genomes to determine when Odaph first appeared phylogenetically. We determined that tooth development in Odaph(+/+) and Odaph(+/C41*) mice was indistinguishable in all respects, so the condition in mice is inherited in a recessive pattern, as it is in humans. Odaph is specifically expressed by ameloblasts starting with the onset of post-secretory transition and continues until mid-maturation. Based upon histological and ultrastructural analyses, we determined that the secretory stage of amelogenesis is not affected in Odaph(C41*/C41*) mice. The enamel layer achieves a normal shape and contour, normal thickness, and normal rod decussation. The fundamental problem in Odaph(C41*/C41*) mice starts during post-secretory transition, which fails to generate maturation stage ameloblasts. At the onset of what should be enamel maturation, a cyst forms that separates flattened ameloblasts from the enamel surface. The maturation stage fails completely.