Transcriptional repression of the Dspp gene leads to dentinogenesis imperfecta phenotype in Col1a1-Trps1 transgenic mice.

[dentinogenesis imperfecta]

Dentinogenesis imperfecta (DGI ) is a hereditary defect of dentin , a calcified tissue that is the most abundant component of teeth . Most commonly , DGI is manifested as a part of osteogenesis imperfecta (OI ) or the phenotype is restricted to dental findings only . In the latter case , DGI is caused by mutations in the DSPP gene , which codes for dentin sialoprotein (DSP ) and dentin phosphoprotein (DPP ). Although these two proteins together constitute the majority of noncollagenous proteins of the dentin , little is known about their transcriptional regulation . Here we demonstrate that mice overexpressing the Trps 1 transcription factor (Col 1 a 1 -Trps 1 mice ) in dentin-producing cells , odontoblasts , present with severe defects of dentin formation that resemble DGI . Combined micro-computed tomography (ÂµCT ) and histological analyses revealed tooth fragility due to severe hypomineralization of dentin and a diminished dentin layer with irregular mineralization in Col 1 a 1 -Trps 1 mice . Biochemical analyses of noncollagenous dentin matrix proteins demonstrated decreased levels of both DSP and DPP proteins in Col 1 a 1 -Trps 1 mice . On the molecular level , we demonstrated that sustained high levels of Trps 1 in odontoblasts lead to dramatic decrease of Dspp expression as a result of direct inhibition of the Dspp promoter by Trps 1 . During tooth development Trps 1 is highly expressed in preodontoblasts , but in mature odontoblasts secreting matrix its expression significantly decreases , which suggests a Trps 1 role in odontoblast development . In these studies we identified Trps 1 as a potent inhibitor of Dspp expression and the subsequent mineralization of dentin . Thus , we provide novel insights into mechanisms of transcriptional dysregulation that leads to DGI .

Diseases
Validation

Diseases presenting "a diminished dentin layer with irregular mineralization in col1a1" symptom

dentinogenesis imperfecta

You can validate or delete this automatically detected symptom