Transcriptional repression of the Dspp gene leads to dentinogenesis imperfecta phenotype in Col1a1-Trps1 transgenic mice.
Bottom Line: On the molecular level, we demonstrated that sustained high levels of Trps1 in odontoblasts lead to dramatic decrease of Dspp expression as a result of direct inhibition of the Dspp promoter by Trps1.During tooth development Trps1 is highly expressed in preodontoblasts, but in mature odontoblasts secreting matrix its expression significantly decreases, which suggests a Trps1 role in odontoblast development.Thus, we provide novel insights into mechanisms of transcriptional dysregulation that leads to DGI.
Affiliation: Institute of Oral Health Research, Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA. email@example.comShow MeSH
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Mentions: In contrast to DGI-I, in which both bone and dentin are affected, presentation of DGI-II and DGI-III is restricted to dental abnormalities. These forms of DGI are caused by mutations in the DSPP gene. The DSPP gene encodes a protein that is proteolytically processed to form DSP and DPP, which are the most abundant noncollagenous proteins in the dentin matrix. To understand the molecular basis of abnormal dentin formation in Col1a1-Trps1 mice, we compared the relative abundance of DSP, DPP, and other SIBLING proteins in the dentin matrices between WT and transgenic animals.30–32 These analyses showed dramatically reduced levels of DPP in transgenic animals (Fig. 3A). At the same time, levels of the N-terminal fragment of DMP1 showed no apparent differences as evaluated by Stains-All staining. Since DSP is less sensitive to Stains-All staining, we compared levels of DSP between WT and transgenic mice by Western blot. These analyses also showed dramatically decreased levels of DSP (Fig. 3B).
Affiliation: Institute of Oral Health Research, Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA. firstname.lastname@example.org