Breuer, Maximillian; Rummier, Maximillian; Zaouter, Charlotte; Willie, Bettina et Patten, Shunmoogum A. . Abnormal spine development and highly mineralized inclusions in vertebrae in a zebrafish model of CHARGE syndrome In: 11e European Zebrafish Meeting, 26-27 October 2020, virtuel.
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CHARGE syndrome is caused by mutations in the chromatin remodeller, CHD7. CHARGE patients, among other symptoms, present with features of idiopathic scoliosis in over 60 % of cases, reduced bone mineral density and osteopenia. Effective disease models are sparse, and the underlying mechanisms remain elusive. Here, we detect and quantitatively analyze skeletal abnormalities in adult chd7-/- zebrafish and young larvae. Our study is the first to identify that young chd7-/- larvae present with scoliosis and kyphosis already at 9 dpf. Gene expression analysis confirmed the significant reduction of osteoblast markers and a delay in vertebrae mineralization. Using MicroCT analyses, we further characterized structural abnormalities in adult chd7-/- fish. All structural entities of the spine, Weberian apparatus, precaudal vertebrae and caudal vertebrae show altered morphology along with highly variable bone mineral density and bone volume. Strikingly, in chd7-/- fish we observed highly mineralized inclusions in the vertebral structure. Finally, we detected a specific depletion in the expression of col2a1a in vertebral cartilage along with a significantly reduced number of chondrocytes. Our study is the first to elucidate the mechanisms underlying spinal development in both larvae and adult chd7-/- zebrafish resulting in decreased spinal integrity. To investigate the underlying pathways of spinal deformities in CHARGE syndrome, the chd7-/- zebrafish will be greatly advantageous
| Type de document: | Document issu d'une conférence ou d'un atelier |
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| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 14 juill. 2021 15:44 |
| Dernière modification: | 14 juill. 2021 15:44 |
| URI: | https://espace.inrs.ca/id/eprint/11860 |
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