ZFIN ID: ZDB-PUB-141007-7
Kinesin family member 6 (kif6) is necessary for spine development in zebrafish
Buchan, J.G., Gray, R.S., Gansner, J.M., Alvarado, D.M., Burgert, L., Gitlin, J.D., Gurnett, C.A., Goldsmith, M.I.
Date: 2014
Source: Developmental dynamics : an official publication of the American Association of Anatomists   243(12): 1646-57 (Journal)
Registered Authors: Gitlin, Jonathan D., Goldsmith, Matt, Gray, Ryan
Keywords: Danio rerio, kinesin, scoliosis
MeSH Terms:
  • Animals
  • Codon, Nonsense
  • Disease Models, Animal
  • Frameshift Mutation
  • Humans
  • Kinesin/genetics
  • Kinesin/metabolism*
  • Phenotype
  • Scoliosis/embryology*
  • Scoliosis/genetics
  • Spine/embryology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 25283277 Full text @ Dev. Dyn.
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ABSTRACT
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 (kif6(gw326) ) 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 kif6(gw326) mutants. Conclusions: Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.
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