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Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta.
J Dent Res. 2019 07; 98(8):912-919.JD

Abstract

Dentin sialophosphoprotein (DSPP) is an extracellular matrix protein highly expressed by odontoblasts in teeth. DSPP mutations in humans may cause dentinogenesis imperfecta (DGI), an autosomal dominant dentin disorder. We recently generated a mouse model (named "DsppP19L/+ mice") that expressed a mutant DSPP in which the proline residue at position 19 was replaced by a leucine residue. We found that the DsppP19L/+ and DsppP19L/P19L mice at a younger age displayed a tooth phenotype resembling human DGI type III characterized by enlarged dental pulp chambers, while the teeth of older DsppP19L/+ and DsppP19L/P19L mice had smaller dental pulp chambers mimicking DGI type II. The teeth of DsppP19L/+ and DsppP19L/P19L mice had a narrower pulp chamber roof predentin layer, thinner pulp chamber roof dentin, and thicker pulp chamber floor dentin. In addition, these mice also had increased enamel attrition, accompanied by excessive deposition of peritubular dentin. Immunohistochemistry, in situ hybridization, and real-time polymerase chain reaction analyses showed that the odontoblasts in both DsppP19L/+ and DsppP19L/P19L mice had reduced DSPP expression, compared to the wild-type mice. We also observed that the levels of DSPP expression were much higher in the roof-forming odontoblasts than in the floor-forming odontoblasts in the wild-type mice and mutant mice. Moreover, immunohistochemistry showed that while the immunostaining signals of dentin sialoprotein (N-terminal fragment of DSPP) were decreased in the dentin matrix, they were remarkably increased in the odontoblasts of the DsppP19L/+ and DsppP19L/P19L mice. Consistently, our in vitro studies showed that the secretion of the mutant DSPP was impaired and accumulated within endoplasmic reticulum. These findings suggest that the dental phenotypes of the mutant mice were associated with the intracellular retention of the mutant DSPP in the odontoblasts of the DSPP-mutant mice.

Authors+Show Affiliations

1 Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA.1 Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA.1 Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA.1 Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA.1 Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA.1 Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, Dallas, TX, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

31173534

Citation

Liang, T, et al. "Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta." Journal of Dental Research, vol. 98, no. 8, 2019, pp. 912-919.
Liang T, Zhang H, Xu Q, et al. Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta. J Dent Res. 2019;98(8):912-919.
Liang, T., Zhang, H., Xu, Q., Wang, S., Qin, C., & Lu, Y. (2019). Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta. Journal of Dental Research, 98(8), 912-919. https://doi.org/10.1177/0022034519854029
Liang T, et al. Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta. J Dent Res. 2019;98(8):912-919. PubMed PMID: 31173534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta. AU - Liang,T, AU - Zhang,H, AU - Xu,Q, AU - Wang,S, AU - Qin,C, AU - Lu,Y, Y1 - 2019/06/07/ PY - 2019/6/8/pubmed PY - 2020/7/16/medline PY - 2019/6/8/entrez KW - extracellular matrix KW - genetics KW - mineralized tissue/development KW - odontoblast(s) KW - odontogenesis KW - tooth development SP - 912 EP - 919 JF - Journal of dental research JO - J Dent Res VL - 98 IS - 8 N2 - Dentin sialophosphoprotein (DSPP) is an extracellular matrix protein highly expressed by odontoblasts in teeth. DSPP mutations in humans may cause dentinogenesis imperfecta (DGI), an autosomal dominant dentin disorder. We recently generated a mouse model (named "DsppP19L/+ mice") that expressed a mutant DSPP in which the proline residue at position 19 was replaced by a leucine residue. We found that the DsppP19L/+ and DsppP19L/P19L mice at a younger age displayed a tooth phenotype resembling human DGI type III characterized by enlarged dental pulp chambers, while the teeth of older DsppP19L/+ and DsppP19L/P19L mice had smaller dental pulp chambers mimicking DGI type II. The teeth of DsppP19L/+ and DsppP19L/P19L mice had a narrower pulp chamber roof predentin layer, thinner pulp chamber roof dentin, and thicker pulp chamber floor dentin. In addition, these mice also had increased enamel attrition, accompanied by excessive deposition of peritubular dentin. Immunohistochemistry, in situ hybridization, and real-time polymerase chain reaction analyses showed that the odontoblasts in both DsppP19L/+ and DsppP19L/P19L mice had reduced DSPP expression, compared to the wild-type mice. We also observed that the levels of DSPP expression were much higher in the roof-forming odontoblasts than in the floor-forming odontoblasts in the wild-type mice and mutant mice. Moreover, immunohistochemistry showed that while the immunostaining signals of dentin sialoprotein (N-terminal fragment of DSPP) were decreased in the dentin matrix, they were remarkably increased in the odontoblasts of the DsppP19L/+ and DsppP19L/P19L mice. Consistently, our in vitro studies showed that the secretion of the mutant DSPP was impaired and accumulated within endoplasmic reticulum. These findings suggest that the dental phenotypes of the mutant mice were associated with the intracellular retention of the mutant DSPP in the odontoblasts of the DSPP-mutant mice. SN - 1544-0591 UR - https://www.unboundmedicine.com/medline/citation/31173534/Mutant_Dentin_Sialophosphoprotein_Causes_Dentinogenesis_Imperfecta_ L2 - https://journals.sagepub.com/doi/10.1177/0022034519854029?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -