Kinesin family member 6 (kif6) is necessary for spine development in zebrafish

• Published in: Developmental dynamics 2014-12, Vol.243 (12), p.1646-1657
• Main Authors: Buchan, Jillian G., Gray, Ryan S., Gansner, John M., Alvarado, David M., Burgert, Lydia, Gitlin, Jonathan D., Gurnett, Christina A., Goldsmith, Matthew I.
• Format: Article
• Language: English
• Subjects: Animals; Codon, Nonsense; Danio rerio; Disease Models, Animal; Frameshift Mutation; Humans; kinesin; Kinesin - genetics; Kinesin - metabolism; Phenotype; scoliosis; Scoliosis - embryology; Scoliosis - genetics; Spine - embryology; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.24208

Background: 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. Results: 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. Conclusions: Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis. Developmental Dynamics 243:1646–1657, 2014. © 2014 Wiley Periodicals, Inc. Key Findings High throughput whole‐genome sequencing is an effective method for cloning zebrafish mutants. Loss of kif6 in zebrafish results in scoliosis without an increase in vertebral anomalies. Zebrafish are a valuable forward genetic model for investigating vertebral development and stability.