Active and Passive Mechanical Deficits Precede Spinal Curvature in a Zebrafish Model of Idiopathic Scoliosis

Although biomechanical imbalance has long been proposed to contribute to scoliosis, the early physiological states that precede curvature onset remain poorly understood. Here, we investigated this problem using zebrafish uts2r3 mutants, which develop fully penetrant juvenile-onset spinal curvature following disruption of urotensin signaling.

Transcriptomic analysis before curvature revealed altered expression of muscle-associated genes, suggesting that Uts2r3 influences axial muscle development or function. However, immunofluorescence, birefringence imaging, and quantitative analysis of myotome morphology showed that mutants lack overt muscle architectural defects or dystrophic pathology. By contrast, direct measurements of isolated larval trunks revealed pre-curvature biomechanical abnormalities: namely, uts2r3 mutants generated reduced active force following electrical stimulation while also exhibiting increased passive resistance to stretch.