PUBLICATION
A Zebrafish Mutant in the Extracellular Matrix Protein Gene efemp1 as a Model for Spinal Osteoarthritis
- Authors
- Raman, R., Bahri, M.A., Degueldre, C., Caetano da Silva, C., Sanchez, C., Ostertag, A., Collet, C., Cohen-Solal, M., Plenevaux, A., Henrotin, Y., Muller, M.
- ID
- ZDB-PUB-240111-10
- Date
- 2023
- Source
- Animals : an open access journal from MDPI 14(1): (Journal)
- Registered Authors
- Muller, Marc
- Keywords
- ECM, efemp1, notochord, osteoarthritis, skeletal development, vertebra, zebrafish
- MeSH Terms
- none
- PubMed
- 38200805 Full text @ Animals (Basel)
Citation
Raman, R., Bahri, M.A., Degueldre, C., Caetano da Silva, C., Sanchez, C., Ostertag, A., Collet, C., Cohen-Solal, M., Plenevaux, A., Henrotin, Y., Muller, M. (2023) A Zebrafish Mutant in the Extracellular Matrix Protein Gene efemp1 as a Model for Spinal Osteoarthritis. Animals : an open access journal from MDPI. 14(1):.
Abstract
Osteoarthritis is a degenerative articular disease affecting mainly aging animals and people. The extracellular matrix protein Efemp1 was previously shown to have higher turn-over and increased secretion in the blood serum, urine, and subchondral bone of knee joints in osteoarthritic patients. Here, we use the zebrafish as a model system to investigate the function of Efemp1 in vertebrate skeletal development and homeostasis. Using in situ hybridization, we show that the efemp1 gene is expressed in the brain, the pharyngeal arches, and in the chordoblasts surrounding the notochord at 48 hours post-fertilization. We generated an efemp1 mutant line, using the CRISPR/Cas9 method, that produces a severely truncated Efemp1 protein. These mutant larvae presented a medially narrower chondrocranium at 5 days, which normalized later at day 10. At age 1.5 years, µCT analysis revealed an increased tissue mineral density and thickness of the vertebral bodies, as well as a decreased distance between individual vertebrae and ruffled borders of the vertebral centra. This novel defect, which has, to our knowledge, never been described before, suggests that the efemp1 mutant represents the first zebrafish model for spinal osteoarthritis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping