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

Dev Dyn. 2014 Dec;243(12):1646-57. doi: 10.1002/dvdy.24208. Epub 2014 Oct 20.

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.

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*

Substances

  • Codon, Nonsense
  • Zebrafish Proteins
  • Kinesin