Kinesin family member 6 (kif6) is necessary for spine development in zebrafish
Buchan, Jillian G.
Gray, Ryan S.
Gansner, John M.
Alvarado, David M.
Gitlin, Jonathan D.
Gurnett, Christina A.
Goldsmith, Matthew I.
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Idiopathic scoliosis is a form of spinal deformity that affects 2–3% of children and results in curvature of the spine without structural defects of the vertebral units. The pathogenesis of idiopathic scoliosis remains poorly understood, in part due to the lack of a relevant animal model. We performed a forward mutagenesis screen in zebrafish to identify new models for idiopathic scoliosis. We isolated a recessive zebrafish mutant, called skolios, which develops isolated spinal curvature that arises independent of vertebral malformations. Using meiotic mapping and whole genome sequencing, we identified a nonsense mutation in kinesin family member 6 (kif6gw326) unique to skolios mutants. Three additional kif6 frameshift alleles (gw327, gw328, gw329) were generated with transcription activator-like effector nucleases (TALENs). Zebrafish homozygous or compound heterozygous for kif6 frameshift mutations developed a scoliosis phenotype indistinguishable from skolios mutants, confirming that skolios is caused by the loss of kif6. Although kif6 may play a role in cilia, no evidence for cilia dysfunction was seen in kif6gw326 mutants. Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.
Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Developmental Dynamics 243 (2014): 1646–1657, doi:10.1002/dvdy.24208.
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