A Zebrafish Mutant in the Extracellular Matrix Protein Gene <i>efemp1</i> as a Model for Spinal Osteoarthritis
Ratish Raman | Mohamed Ali Bahri | Christian Degueldre | Caroline Caetano da Silva | Christelle Sanchez | Agnes Ostertag | Corinne Collet | Martine Cohen-Solal | Alain Plenevaux | Yves Henrotin | Marc Muller
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 <i>efemp1</i> gene is expressed in the brain, the pharyngeal arches, and in the chordoblasts surrounding the notochord at 48 hours post-fertilization. We generated an <i>efemp1</i> 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 <i>efemp1</i> mutant represents the first zebrafish model for spinal osteoarthritis.
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