PT - JOURNAL ARTICLE AU - Imke A.K. Fiedler AU - Felix N. Schmidt AU - Christine Plumeyer AU - Petar Milovanovic AU - Roberta Gioia AU - Francesca Tonelli AU - Antonella Forlino AU - Björn Busse TI - Severely impaired bone material quality in <em>Chihuahua</em> zebrafish resembles classical dominant human osteogenesis imperfecta AID - 10.1101/251652 DP - 2018 Jan 01 TA - bioRxiv PG - 251652 4099 - http://biorxiv.org/content/early/2018/01/22/251652.short 4100 - http://biorxiv.org/content/early/2018/01/22/251652.full AB - Abstract 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 dominant OI. Similar to human severe OI type III, Chi/+ show skeletal deformities, altered mineralization patterns and a smaller body size. Using a multimodal approach targeting bone quality parameters, this study aims at quantifying the changes in bone morphology, structure and tissue composition of Chi/+ at multiple length scales. Morphological changes were assessed with high-resolution micro-CT imaging and showed that the vertebrae in Chi/+ had a significantly smaller size, thinner cortical shell and distorted shape. Tissue composition in vertebrae was investigated with quantitative backscattered electron microscopy and Fourier-transform infrared spectroscopy, showing higher mean calcium content, greater matrix porosity, as well as lower mineral crystallinity and collagen maturity in comparison to controls. This study provides comprehensive quantitative data on bone quality indices in Chi/+ and thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant osteogenesis imperfecta, both at the whole bone level and the tissue level.