Enamel Defects Associated With Mutant Dentin Sialophosphoprotein (DSPP)

Objectives: Dentin sialophosphoprotein (DSPP) is predominantly expressed in odontoblasts and transiently expressed in early secretory ameloblasts. Mutations in the DSPP gene result in non-syndromic dentinogenesis imperfecta/Dentin dysplasia in humans. We previously generated a knockin mouse model expressing a mouse equivalent (Dspp p.19L) of human mutant DSPP (p.P17L) (referred to as “Dspp^P19L/+”). In this study, we analyzed the pathogenic effects of the mutant DSPP-P19L on enamel development in the Dspp^P19L/+ and Dspp^P19L/+ mice.
Methods: Plain X-ray radiography, micro-Computed Tomography (µCT) and Hematoxylin & eosin (H&E) staining were performed to characterize the dental phenotypes of the Dspp^P19L/+ and Dspp^P19L/P19L mice. In situ hybridization (ISH) and immunohistochemistry (IHC) were conducted to analyze the expressions of DSPP in the ameloblasts at the transcript and protein levels, respectively.
Results: Plain X-ray radiography showed that the Dspp^P19L/+ and Dspp^P19L/P19L (together called “DSPP mutant”) mice displayed severe occlusal tooth wear with age, compared to the wild-type (Dspp^+/+) littermates. Micro-CT analyses demonstrated that the DSPP-mutant mice developed an enlarged dental pulp chamber by postnatal 3 weeks, and then acquired a small dental pulp chamber with age. The DSPP mutant mice had less amount of enamel and reduced enamel density, compared to the age- and gender-matched wild-type mice. Moreover, the DSPP mutant mice suffered from a rapid loss of enamel over age. ISH revealed that DSPP expression was markedly reduced in the early secretory ameloblasts in the 1-week-old DSPP mutant mice, compared to the age-matched wild-type mice. In contrast, IHC showed that DSP immunostaining signals were much stronger in the early secretory ameloblasts in the DSPP mutant mice than in the wild-type mice.
Conclusions: The enamel defects observed in the Dspp^P19L/+ and Dspp^P19L/P19L mice may be associated with increased intracellular retention of the mutant DSPP in the early secretory ameloblasts.