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Enamel Defects Associated With Dentin Sialophosphoprotein Mutation in Mice
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 muta...
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Published in: | Frontiers in physiology 2021-09, Vol.12, p.724098-724098 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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 (μCT) 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, μCT 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 |
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ISSN: | 1664-042X 1664-042X |
DOI: | 10.3389/fphys.2021.724098 |