Skeletal malformations of Meox1-deficient zebrafish resemble human Klippel-Feil syndrome

Klippel-Feil syndrome is a congenital vertebral anomaly, which is characterised by the fusion of at least two cervical vertebrae and a clinically broad set of symptoms, including congenital scoliosis and elevated scapula (Sprengel's deformity). Klippel-Feil syndrome is associated with mutations in MEOX1. The zebrafish mutant choker (cho) carries a mutation in its orthologue, meox1. Although zebrafish is being increasingly employed as fidelitous models of human spinal disease, the vertebral column of Meox1-deficient fish has not been assessed for defects. Here, we describe the skeletal defects of meox1^cho mutant zebrafish utilising alizarin red to stain bones and chemical maceration of soft tissue to detect fusions in an unbiased manner. Obtained data reveal that meox1^cho mutants feature aspects of a number of described symptoms of patients who suffer from Klippel-Feil syndrome and have mutations in MEOX1. These include vertebral fusion, congenital scoliosis and an asymmetry of the pectoral girdle, which resembles Sprengel's deformity. Thus, the meox1^cho mutant zebrafish may serve as a useful tool to study the pathogenesis of the symptoms associated with Klippel-Feil syndrome.