Journal of Orthopedic Surgery and Rehabilitation

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Development of Zebrafish (Danio rerio) as a natural model system for studying scoliosis

Background: Idiopathic scoliosis in humans is an abnormal 3-dimensional curvature of the spine with unknown cause. The lack of a model system with naturally occurring spinal curvatures has hindered research on the etiology of idiopathic scoliosis. Recently, it has become clear that zebrafish and other fish species exhibit spinal curvatures similar to those found in humans, making them a good animal model system for studying idiopathic scoliosis. Methods: Founder fish with spinal curvatures were outcrossed with a wild type zebrafish line (AB) and the resulting siblings (F1 generation) crossed and their offspring (F2 generation) examined for signs of spinal curvature beginning at 14 days post fertilization (dpf). Spinal curvatures of the affected fish were visualized using either a Faxitron or by Alizarian red staining of the skeletons and the curvature measured from the resulting images in the thoracic, thoracolumbar, or lumbar regions. Affected and normal zebrafish were sectioned and stained with hemotoxylin and eosin. Findings: The degrees of curvatures in affected zebrafish ranged from 18° to 40°. Histological data demonstrated structural changes as compared to normal fish spine. Out of 212 individuals in the F2 generation 28, or 13.2%, were observed to have spinal deformities at 21 dpf. Importantly, we did not observe spinal deformities in the F1 generation fish and similar age wild type fish, indicating the observed spinal deformities were due to a recessive mutation(s). Conclusion: We have noticed several fish in our zebrafish colony with spinal curvatures reminiscent of human idiopathic scoliosis. We suspect that “scoliosis” in these zebrafish results from mutation(s) in the zebrafish genome. And these fish can be the source of a zebrafish line in which the offspring exhibit a predictable frequency of scoliosis which can be used to study the etiology and progression of scoliosis.

Author(s): Tomasiewicz HG, Johnson BA, Liu XC, North P