Enamel Defects Associated With Dentin Sialophosphoprotein Mutation in Mice

Area of Science:

• Oral Biology
• Developmental Biology
• Biochemistry

Background:

• Dentin sialophosphoprotein (DSPP) is crucial for tooth development, primarily in dentin formation.
• Mutations in DSPP are linked to dentinogenesis imperfecta (DGI), affecting dentin structure.
• DSPP is transiently expressed in presecretory ameloblasts, suggesting a potential role in enamel development.

Purpose of the Study:

• To investigate the pathogenic effects of mutant P19L-DSPP on enamel development in a knockin mouse model.
• To analyze the impact of mutant DSPP on enamel structure, volume, and density during amelogenesis.
• To explore the cellular mechanisms underlying DSPP-associated enamel defects.

Main Methods:

• Generation of a DSPP knockin mouse model (Dspp) expressing a human-equivalent mutation (p.P19L).
• Micro-Computed Tomography (μCT) to assess enamel volume and density in incisors and molars.
• Scanning Electron Microscopy (SEM) with acid-etching and backscattered imaging to analyze enamel rod structure.
• In situ hybridization and immunohistochemistry to examine DSPP mRNA and protein expression in ameloblasts.

Main Results:

• Dspp mice exhibited significantly reduced enamel volume and density in mandibular incisors and molars.
• SEM analysis revealed abnormal enamel rod formation, with Dspp mice showing particulate structures instead of discernible rods.
• While incisor enamel structure improved over time in Dspp mice, molar enamel remained poorly organized.
• DSPP mRNA levels were reduced, but mutant DSPP protein accumulated intracellularly within presecretory ameloblasts.

Conclusions:

• Mutant P19L-DSPP protein induces developmental enamel defects in mice.
• Intracellular retention of mutant DSPP in presecretory ameloblasts is a potential mechanism for these enamel abnormalities.
• These findings highlight a novel role for DSPP in enamel matrix formation and maturation.