Breuer, Maximillian; Rummier, Maximillian; Zaouter, Charlotte; Willie, Bettina et Patten, Shunmoogum A. . Abnormal skeletal development and highly mineralized inclusions in vertebrae in a zebrafish model of CHARGE syndrome In: Colloque en ligne du Centre d’Excellence en Recherche sur les Maladies Orphelines-Fondation Courtois, 23 novembre 2020, virtuel.
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CHARGE syndrome is caused primarily by mutations in the chromatin remodeller, CHD7. CHARGE patients, among other symptoms, present with craniofacial abnormalities. Furthermore, patients display 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 craniofacial dysmorphism, as well as scoliosis and kyphosis. Gene expression analysis confirmed the significant reduction of osteoblast markers and Runx2 targets. Using MicroCT analyses, we further characterized structural abnormalities in adult chd7-/- fish. All structural entities of the skeleton i.e., skull, Weberian apparatus, precaudal vertebrae and caudal vertebrae show significantly 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 cartilage along with a significantly reduced number of chondrocytes.
Our study is the first to elucidate the mechanisms underlying skeletal development in both larvae and adult chd7-/- zebrafish resulting in craniofacial and spinal deformities. To investigate the underlying pathways of skeletal 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 15:58 |
| Dernière modification: | 13 juin 2023 21:57 |
| URI: | https://espace.inrs.ca/id/eprint/11797 |
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