Craniofacial and Dental Defects in the Col1a1Jrt/+ Mouse Model of Osteogenesis Imperfecta

J Dent Res. 2016 Jul;95(7):761-8. doi: 10.1177/0022034516637045. Epub 2016 Mar 7.

Abstract

Certain mutations in the COL1A1 and COL1A2 genes produce clinical symptoms of both osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) that include abnormal craniofacial growth, dental malocclusion, and dentinogenesis imperfecta. A mouse model (Col1a1(Jrt)/+) was recently developed that had a skeletal phenotype and other features consistent with moderate-to-severe OI and also with EDS. The craniofacial phenotype of 4- and 20-wk-old Col1a1(Jrt)/+ mice and wild-type littermates was assessed by micro-computed tomography (µCT) and morphometry. Teeth and the periodontal ligament compartment were analyzed by µCT, light microscopy/histomorphometry, and electron microscopy. Over time, at 20 wk, Col1a1(Jrt)/+ mice developed smaller heads, a shortened anterior cranial base, class III occlusion, and a mandibular side shift with shorter morphology in the masticatory region (maxilla and mandible). Col1a1(Jrt)/+ mice also had changes in the periodontal compartment and abnormalities in the dentin matrix and mineralization. These findings validate Col1a1(Jrt)/+ mice as a model for OI and EDS in humans.

Keywords: Ehlers-Danlos syndrome; bone; bone development; craniofacial abnormalities; dentin; tooth calcification.

MeSH terms

  • Animals
  • Collagen Type I / genetics
  • Collagen Type I / physiology*
  • Collagen Type I, alpha 1 Chain
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • Disease Models, Animal
  • Ehlers-Danlos Syndrome / genetics
  • Ehlers-Danlos Syndrome / pathology
  • Mice
  • Mice, Mutant Strains
  • Microscopy
  • Microscopy, Electron
  • Osteogenesis Imperfecta / genetics
  • Osteogenesis Imperfecta / pathology*
  • Periodontal Ligament / abnormalities
  • Periodontal Ligament / pathology
  • Tooth Abnormalities / genetics*
  • Tooth Abnormalities / pathology
  • X-Ray Microtomography

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain