| First Author | Liang T | Year | 2021 |
| Journal | Front Physiol | Volume | 12 |
| Pages | 724098 | PubMed ID | 34630144 |
| Mgi Jnum | J:312670 | Mgi Id | MGI:6786411 |
| Doi | 10.3389/fphys.2021.724098 | Citation | Liang T, et al. (2021) Enamel Defects Associated With Dentin Sialophosphoprotein Mutation in Mice. Front Physiol 12:724098 |
| abstractText | Dentin sialophosphoprotein (DSPP) is an extracellular matrix protein that is highly expressed in odontoblasts, but only transiently expressed in presecretory ameloblasts during tooth development. We previously generated a knockin mouse model expressing a mouse equivalent (DSPP, p.P19L) of human mutant DSPP (p.P17L; referred to as "Dspp(P19L/+) "), and reported that Dspp(P19L/+) and Dspp(P19L/P19L) mice manifested a dentin phenotype resembling human dentinogenesis imperfecta (DGI). In this study, we analyzed pathogenic effects of mutant P19L-DSPP on enamel development in Dspp(P19L/+) and Dspp(P19L/P19L) mice. Micro-Computed Tomography (muCT) analyses of 7-week-old mouse mandibular incisors showed that Dspp(P19L/P19L) mice had significantly decreased enamel volume and/or enamel density at different stages of amelogenesis examined. Acid-etched scanning electron microscopy (SEM) analyses of mouse incisors demonstrated that, at the mid-late maturation stage of amelogenesis, the enamel of wild-type mice already had apparent decussating pattern of enamel rods, whereas only minute particulates were found in Dspp(P19L/+) mice, and no discernible structures in Dspp(P19L/P19L) mouse enamel. However, by the time that incisor enamel was about to erupt into oral cavity, distinct decussating enamel rods were evident in Dspp(P19L/+) mice, but only poorly-defined enamel rods were revealed in Dspp(P19L/P19L) mice. Moreover, muCT analyses of the mandibular first molars showed that Dspp(P19L/+) and Dspp(P19L/P19L) mice had a significant reduction in enamel volume and enamel density at the ages of 2, 3, and 24weeks after birth. Backscattered and acid-etched SEM analyses revealed that while 3-week-old Dspp(P19L/+) mice had similar pattern of enamel rods in the mandibular first molars as age-matched wild-type mice, no distinct enamel rods were observed in Dspp(P19L/P19L) mice. Yet neither Dspp(P19L/+) nor Dspp(P19L/P19L) mice showed well-defined enamel rods in the mandibular first molars by the age of 24weeks, as judged by backscattered and acid-etched SEM. In situ hybridization showed that DSPP mRNA level was markedly reduced in the presecretory ameloblasts, but immunohistochemistry revealed that DSP/DSPP immunostaining signals were much stronger within the presecretory ameloblasts in Dspp mutant mice than in wild-type mice. These results suggest that mutant P19L-DSPP protein caused developmental enamel defects in mice, which may be associated with intracellular retention of mutant DSPP in the presecretory ameloblasts. |
