Gene Expression Profiles of Wild Type and DSPP Knockout Mouse Teeth
Ko-Chien Wu, Helena H Ritchie.
DSPP knock-out mice exhibited hypomineralized teeth, thin dentin and a large dental pulp chamber, similar to teeth from human patients with dentinogenesis imperfecta III. Systematical examination of teeth from wild-type (wt) and DSPP KO mice revealed developmental abnormalities, such as circular dentin formation within dental pulp cells and altered odontoblast differentiation in DSPP KO mice, even as early as one day after birth. In addition, chondrocyte-like cells were identified in the dental pulp from DSPP KO mice teeth. These studies suggest that the expression of DSPP precursor protein is required for normal odontoblast lineage differentiation and that the absence of DSPP results in the appearance of chondrocyte-like cells. To further understand the undermining mechanisms for the characters of DSPP KO mice, we examined and compared the gene expression profiles between wt and DSPP KO mice via Real Time PCR (RT-PCR) and immunohistochemical images. In DSPP KO mouse incisors at 21-day old, there was no DSPP expression and major odontoblast lineage markers (Dmp1 and Osx) were down-regulated. Runx2 expression was down regulated in differentiated odontoblasts in wt incisors but RT-PCR analyses of DSPP KO mice showed up regulation of Runx2 expression. Furthermore, in DSPP KO incisors, expressing increased amounts of chondrocyte lineage transcription factors Sox9 and Runx2. Immunochemical studies with Runx2 expression and Osx expression support RT-PCR data. Therefore, gene expression profiles support the phenotypes of wt and DSPP KO mice. These findings support that DSPP is required for maintaining normal odontoblast lineage and absence of DSPP promote the development of chondrocyte cell fate.