Transforming growth factor (TGF)-beta1 is expressed in developing tooth from the initiation stage through adulthood. Odontoblast-specific expression of
TGF-beta1 in the tooth continues throughout life; however, the precise
biological functions of this
growth factor in the odontoblasts are not clearly understood. Herein, we describe the generation of transgenic mice that overexpress active
TGF-beta1 predominantly in the odontoblasts. Teeth of these mice show a significant reduction in the tooth mineralization, defective dentin formation, and a relatively high branching of dentinal tubules. Dentin extracellular matrix components such as type I and III
collagens are increased and deposited abnormally in the dental pulp, similar to the hereditary human tooth disorders such as
dentin dysplasia and
dentinogenesis imperfecta.
Calcium, one of the crucial inorganic components of mineralization, is also apparently increased in the transgenic mouse teeth. Most importantly, the expression of
dentin sialophosphoprotein (dspp), a candidate gene implicated in
dentinogenesis imperfecta II (MIM 125420), is significantly down-regulated in the transgenic teeth. Our results provide in vivo evidence suggesting that
TGF-beta1 mediated expression of dspp is crucial for dentin mineralization. These findings also provide for the first time a direct experimental evidence indicating that decreased dspp gene expression along with the other cellular changes in odontoblasts may result in human hereditary dental disorders like
dentinogenesis imperfecta II (MIM 125420) and
dentin dysplasia (MIM 125400 and 125420).