Trps1 Deficiency in Mice Recapitulates Microdontia Phenotype of the Trichorhinophalangeal Syndrome

Objectives: Trichorhinophalangeal syndrome (TRPS) is an autosomal dominant craniofacial and skeletal dysplasia caused by mutations in the TRPS1 gene coding for a GATA-type transcription factor, Trps1. Trps1 is highly expressed in dental mesenchyme throughout all stages of mouse tooth development, suggesting a role in tooth formation. Consistently, TRPS patients present with dental abnormalities that include supernumeratity, microdontia, malocclusion and delayed tooth eruption. However, previous analyses of Trps1 mutant mice did not detect any aberrations in tooth number. Here, we address the microdontia phenotype in Trps1 deficiency.
Methods: Trps1 mutant mice carrying an in frame deletion of the exon 5 coding for a DNA binding domain were analyzed. Micro-CT was used to compare tooth size and morphology in 8wk old Trps1^+/- and WT mice. Histomorphometry was used to measure size of tooth organs in E18.5 Trps1^-/- and WT mice. Cell proliferation and expression of proteins involved in tooth formation were analyzed by immunohistochemistry.
Results: No differences in tooth size were detected between 8wk old Trps1^+/- and WT mice, however, molar organs of Trps1^-/- mice are smaller than WT littermates and demonstrate lower structural complexity. Significantly fewer proliferating cells were detected in dental epithelium and mesenchyme of Trps1^-/- developing molars then in WT mice. Furthermore, in Trps1^-/- molar organs, altered expression of major osteogenic transcription factors Runx2 and Sp7 was detected compared to WT.
Conclusions: Our results suggest that Trps1 is involved in regulation of tooth size by supporting proliferation of cells in dental mesenchyme and epithelium during tooth development. Additionally, Trps1 regulates the spatial expression pattern of genes involved in tooth formation.