DSPP dosage affects tooth development and dentin mineralization

Area of Science:

• Biochemistry
• Developmental Biology
• Genetics

Background:

• Dentin sialophosphoprotein (DSPP) is crucial for dentin formation, and its absence causes dentinogenesis imperfecta type III.
• DSPP knock-out (KO) mice exhibit thin dentin, enlarged pulp chambers, and abnormal cellular interactions.

Purpose of the Study:

• To investigate the influence of DSPP gene dosage on tooth development and dentin formation.
• To rescue DSPP deficiency using a bacterial artificial chromosome (BAC) transgene expressing DSPP.

Main Methods:

• Generated BAC-DSPP transgenic mice on a DSPP KO background.
• Characterized two strains (Strain A and Strain B) with varying DSPP expression levels.
• Assessed dentin mineral density and thickness using microCT analysis.

Main Results:

• Strain A mice, with near wild-type DSPP expression, showed complete rescue of dentin defects, including normal thickness and mineral density.
• Strain B mice, with 10% DSPP mRNA and 5% phosphophoryn (PP) protein, partially rescued the defects, improving mineral density over KO mice.
• DSPP dosage in Strain A restored epithelial-mesenchymal interactions and odontoblast maintenance; Strain B showed only partial rescue.

Conclusions:

• DSPP gene dosage is critical for normal tooth development and dentin biomineralization.
• Restoration of DSPP, even at partial levels, can ameliorate dentinogenesis imperfecta-like phenotypes.
• BAC-DSPP transgenesis is a viable strategy for studying DSPP function and potential therapeutic interventions.