Dental abnormalities in a mouse model for craniometaphyseal dysplasia

J Dent Res. 2013 Feb;92(2):173-9. doi: 10.1177/0022034512468157. Epub 2012 Nov 15.


Mice carrying a knock-in mutation (Phe377del) in the Ank gene replicate many skeletal characteristics of human craniometaphyseal dysplasia, including hyperostotic mandibles. Ank (KI/KI) mice have normal morphology of erupted molars and incisors but excessive cementum deposition with increased numbers of Ibsp- and Dmp1-positive cells on root surfaces. The cervical loops of adult Ank (KI/KI) lower incisors are at the level of the third molars, while they are close to the mandibular foramen in Ank (+/+) mice. Furthermore, Ank (KI/KI) incisors show decreased eruption rates, decreased proliferation of odontoblast precursors, and increased cell apoptosis in the stellate reticulum. However, their capability for continuous elongation is not compromised. Quantification of TRAP-positive cells in the apical ends of Ank (KI/KI) incisors revealed decreased osteoclast numbers and osteoclast surfaces. Bisphosphonate injections in Ank (+/+) mice replicate the Ank (KI/KI) incisor phenotype. These results and a comparison with the dental phenotype of Ank loss-of-function mouse models suggest that increased cementum thickness may be caused by decreased extracellular PPi levels and that the incisor phenotype is likely due to hyperostosis of mandibles, which distinguishes Ank (KI/KI) mice from the other Ank mouse models.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Bone Density Conservation Agents / pharmacology
  • Bone Diseases, Developmental / genetics
  • Bone Diseases, Developmental / pathology*
  • Bone Remodeling / drug effects
  • Bone Remodeling / physiology
  • Cell Count
  • Cell Proliferation
  • Cell Shape
  • Craniofacial Abnormalities / genetics
  • Craniofacial Abnormalities / pathology*
  • Dental Cementum / abnormalities
  • Diphosphonates / pharmacology
  • Disease Models, Animal
  • Extracellular Matrix Proteins / analysis
  • Gene Knock-In Techniques
  • Hyperostosis / genetics
  • Hyperostosis / pathology*
  • Hypertelorism / genetics
  • Hypertelorism / pathology*
  • Incisor / abnormalities
  • Integrin-Binding Sialoprotein / analysis
  • Mandibular Diseases / genetics
  • Mandibular Diseases / pathology
  • Mice
  • Mice, Transgenic
  • Molar / abnormalities
  • Odontoblasts / pathology
  • Organ Culture Techniques
  • Osteoclasts / pathology
  • Phenotype
  • Phosphate Transport Proteins / genetics
  • Tooth Abnormalities / pathology*
  • Tooth Apex / pathology
  • Tooth Eruption / physiology
  • Tooth Root / pathology


  • Bone Density Conservation Agents
  • Diphosphonates
  • Dmp1 protein, mouse
  • Extracellular Matrix Proteins
  • Ibsp protein, mouse
  • Integrin-Binding Sialoprotein
  • Phosphate Transport Proteins
  • ank protein, mouse

Supplementary concepts

  • Schwartz-Lelek syndrome