Aberrant cementum phenotype associated with the hypophosphatemic hyp mouse.
BACKGROUND
Cementogenesis is sensitive to altered local phosphate levels; thus, we hypothesized a cementum phenotype, likely of decreased formation, would be present in the teeth of X-linked hypophosphatemic (Hyp) mice. Mutations in the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (Phex) cause X-linked hypophosphatemia, characterized by rickets, osteomalacia, and hypomineralized dentin formation, a phenotype recapitulated in the Hyp mouse homolog. Here, we report a developmental study of tooth root formation in Hyp mouse molars, focusing on dentin and cementum.


METHODS
Light and transmission electron microscopy were used to study molar tissues from wild-type (WT) and Hyp mice. Demineralized and hematoxylin and eosin-stained tissues at developmental stages 23 to 96 days postcoital (dpc) were examined by light microscopy. Immunohistochemistry methods were used to detect bone sialoprotein (BSP) distribution in Hyp and WT mouse molar tissues, and transmission electron microscopy was used to study similar molar tissues in the non-demineralized state.


RESULTS
Dentin in Hyp mice exhibited mineralization defects by 33 dpc, as expected, but this defect was partially corrected by 96 dpc. In support of our hypothesis, a cementum phenotype was detected using a combination of immunohistochemistry and transmission electron microscopy, which included thinner BSP-positive staining within the cementum, discontinuous mineralization, and a globular appearance compared to WT controls.


CONCLUSIONS
Mutations in the phosphate-regulating Phex gene of the Hyp mouse resulted in defective cementum development.
Fong
H
H
Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA. hfong@u.washington.edu
Chu
E Y
EY
Tompkins
K A
KA
Foster
B L
BL
Sitara
D
D
Lanske
B
B
Somerman
M J
MJ
D000818:Animals; D025021:Cementogenesis / Q000235:genetics*; D003739:Dental Cementum / Q000002:abnormalities* / Q000473:pathology; D003804:Dentin / Q000002:abnormalities / Q000473:pathology; D003810:Dentinogenesis / Q000235:genetics; D053098:Familial Hypophosphatemic Rickets / Q000473:pathology*; D005260:Female; D040181:Genetic Diseases, X-Linked; D005865:Gestational Age; D007150:Immunohistochemistry; D058574:Integrin-Binding Sialoprotein; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D008963:Molar / Q000002:abnormalities / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009805:Odontogenesis / Q000235:genetics; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics; D010641:Phenotype; D012795:Sialoglycoproteins / Q000032:analysis; D014074:Tooth Calcification / Q000235:genetics; D014083:Tooth Germ / Q000002:abnormalities / Q000473:pathology; D014092:Tooth Root / Q000002:abnormalities / Q000473:pathology
C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D012795:Sialoglycoproteins; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506232:Phex protein, mouse