Dspp-KO Mouse

Dspp, short for Dentin sialophosphoprotein, is a gene encoding proteins DSP (dentine sialoprotein) and DPP (dentine phosphoprotein) that are positive regulators of dentine formation [2]. It is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3 (DGI-III) and dentine dysplasia type 2 (DD-II), and is involved in the mineralization of dentine [2]. Additionally, Dspp has been found to be expressed in bone, periodontal tissues, salivary glands, mandibular condylar cartilage, and craniofacial skeleton, indicating its broader role in tissue development and maintenance [1,5,6]. Genetic models, especially mouse models, have been crucial in understanding Dspp's function.

In Dspp knockout (KO) mice, the absence of the gene leads to characteristics consistent with human dentinogenesis imperfecta type III, such as thin dentin, larger pulp chambers with frequent pulp exposure, abnormal epithelial-mesenchymal interactions, and the appearance of chondrocyte-like cells in dental pulp [3]. Dspp-1fs mouse model, generated using CRISPR/Cas9, shows dentin formation analogous to reparative dentin, lacking dentinal tubules, containing cellular debris, and being significantly softer and thinner than normal [4,7]. Dspp+/- mice exhibit temporomandibular joint osteoarthritis (TMJ OA) in a time-dependent manner, with lesions in the mandibular condyle due to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers [5]. Moreover, Dspp knockout mice also present furcation involvement, cementum, and alveolar bone defect, suggesting a role in periodontal tissue formation [1].

In conclusion, Dspp is essential for dentine formation and mineralization, and also plays a role in the development and maintenance of periodontal tissues, craniofacial structures, and the temporomandibular joint. The use of Dspp KO and other mouse models has significantly contributed to understanding its role in these biological processes and associated diseases like dentinogenesis imperfecta, dentine dysplasia, and TMJ OA.

References:

1. Jing, Zhaojun, Chen, Zhibin, Jiang, Yong. 2021. Effects of DSPP Gene Mutations on Periodontal Tissues. In Global medical genetics, 8, 90-94. doi:10.1055/s-0041-1726416. https://pubmed.ncbi.nlm.nih.gov/34430959/

2. Jia, Jie, Bian, Zhuan, Song, Yaling. . The Role of DSPP in Dentine Formation and Hereditary Dentine Defects. In The Chinese journal of dental research, 27, 17-28. doi:10.3290/j.cjdr.b5136791. https://pubmed.ncbi.nlm.nih.gov/38546516/

3. Lim, Dandrich, Wu, Ko-Chien, Lee, Arthur, Saunders, Thomas L, Ritchie, Helena H. 2021. DSPP dosage affects tooth development and dentin mineralization. In PloS one, 16, e0250429. doi:10.1371/journal.pone.0250429. https://pubmed.ncbi.nlm.nih.gov/34038418/

4. Liang, Tian, Hu, Yuanyuan, Zhang, Hong, Hu, Jan C-C, Simmer, James P. 2021. Mouse Dspp frameshift model of human dentinogenesis imperfecta. In Scientific reports, 11, 20653. doi:10.1038/s41598-021-00219-4. https://pubmed.ncbi.nlm.nih.gov/34667213/

5. Liu, Qilin, Zhao, Yitong, Shi, Haibo, Ma, Ning, Sun, Hongchen. 2024. Long-term haplodeficency of DSPP causes temporomandibular joint osteoarthritis in mice. In BMC oral health, 24, 569. doi:10.1186/s12903-024-04320-8. https://pubmed.ncbi.nlm.nih.gov/38745274/

6. Figueredo, Carlos Alberto, Abdelhay, Nancy, Ganatra, Seema, Gibson, Monica Prasad. 2022. The role of Dentin Sialophosphoprotein (DSPP) in craniofacial development. In Journal of oral biology and craniofacial research, 12, 673-678. doi:10.1016/j.jobcr.2022.08.010. https://pubmed.ncbi.nlm.nih.gov/36062256/

7. Liang, Tian, Smith, Charles E, Hu, Yuanyuan, Hu, Jan C-C, Simmer, James P. 2023. Dentin defects caused by a Dspp-1 frameshift mutation are associated with the activation of autophagy. In Scientific reports, 13, 6393. doi:10.1038/s41598-023-33362-1. https://pubmed.ncbi.nlm.nih.gov/37076504/