Severely impaired bone material quality in Chihuahua zebrafish resembles classical dominant human osteogenesis imperfecta

Fiedler, I.A.K., Schmidt, F.N., Wölfel, E.M., Plumeyer, C., Milovanovic, P., Gioia, R., Tonelli, F., Bale, H.A., Jähn, K., Besio, R., Forlino, A., Busse, B.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research   33(8): 1489-1499 (Journal)
Registered Authors
Bone histomorphometry, Bone matrix, Genetic animal models, Osteogenesis imperfecta
MeSH Terms
  • Animals
  • Bone Density
  • Bone and Bones/pathology*
  • Disease Models, Animal
  • Genes, Dominant*
  • Humans
  • Larva/physiology
  • Osteogenesis
  • Osteogenesis Imperfecta/pathology*
  • Phenotype
  • Zebrafish/physiology*
29665086 Full text @ J. Bone Miner. Res.
Excessive skeletal deformations and brittle fractures in the vast majority of patients suffering from osteogenesis imperfecta (OI) are a result of substantially reduced bone quality. Since the mechanical competence of bone is dependent on the tissue characteristics at small length scales, it is of crucial importance to assess how osteogenesis imperfecta manifests at the micro- and nanoscale of bone. In this context, the Chihuahua (Chi/ +) zebrafish, carrying a heterozygous glycine substitution in the α1 chain of collagen type I, has recently been proposed as suitable animal model of classical dominant OI, showing skeletal deformities, altered mineralization patterns and a smaller body size. This study assessed the bone quality properties of Chi/+ at multiple length scales using micro-computed tomography (micro-CT), histomorphometry, quantitative back-scattered electron imaging, Fourier transform infrared spectroscopy, nanoindentation and X-ray microscopy. At the skeletal level, Chi/+ display smaller body size, deformities and fracture calli in the ribs. Morphological changes at the whole bone level showed that the vertebrae in Chi/+ had a smaller size, smaller thickness and distorted shape. At the tissue level, Chi/+ displayed a higher degree of mineralization, lower collagen maturity, lower mineral maturity, altered osteoblast morphology, and lower osteocyte lacunar density compared to WT. The alterations in the cellular, compositional and structural properties of Chi/+ bones bear an explanation for the impaired local mechanical properties, which promote an increase in overall bone fragility in Chi/ +. The quantitative assessment of bone quality in Chi/+ thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant osteogenesis imperfecta. This article is protected by copyright. All rights reserved.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes