Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III.
Dentin sialophosphoprotein (Dspp) is mainly expressed in teeth by the odontoblasts and preameloblasts. The Dspp mRNA is translated into a single protein, Dspp, and cleaved into two peptides, dentin sialoprotein and dentin phosphoprotein, that are localized within the dentin matrix. Recently, mutations in this gene were identified in human dentinogenesis imperfecta II (Online Mendelian Inheritance in Man (OMIM) accession number 125490) and in dentin dysplasia II (OMIM accession number 125420) syndromes. Herein, we report the generation of Dspp-null mice that develop tooth defects similar to human dentinogenesis imperfecta III with enlarged pulp chambers, increased width of predentin zone, hypomineralization, and pulp exposure. Electron microscopy revealed an irregular mineralization front and a lack of calcospherites coalescence in the dentin. Interestingly, the levels of biglycan and decorin, small leucine-rich proteoglycans, were increased in the widened predentin zone and in void spaces among the calcospherites in the dentin of null teeth. These enhanced levels correlate well with the defective regions in mineralization and further indicate that these molecules may adversely affect the dentin mineralization process by interfering with coalescence of calcospherites. Overall, our results identify a crucial role for Dspp in orchestrating the events essential during dentin mineralization, including potential regulation of proteoglycan levels.
Functional Genomics Unit and Gene Targeting Facility, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA. tsreenat@mail.nih.gov
Taduru
T
Sreenath
Tamizchelvi
T
Thyagarajan
Bradford
B
Hall
Glenn
G
Longenecker
Rena
R
D'Souza
Sung
S
Hong
J Tim
JT
Wright
Mary
M
MacDougall
John
J
Sauk
Ashok B
AB
Kulkarni
D000818:Animals; D003804:Dentin / Q000473:pathology / Q000502:physiology; D003811:Dentinogenesis Imperfecta / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016326:Extracellular Matrix Proteins; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins; D011498:Protein Precursors / Q000235:genetics* / Q000502:physiology; D012795:Sialoglycoproteins; D014070:Tooth / Q000473:pathology / Q000502:physiology; D014074:Tooth Calcification / Q000235:genetics; D000099311:Dentin Sialophosphoprotein
D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D011498:Protein Precursors; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein