title: Kinesin family member 6 (kif6) is necessary for spine development in zebrafish.
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.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Jillian G
authors.initials: JG
authors.lastname: Buchan
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Gray
authors.forename: John M
authors.initials: JM
authors.lastname: Gansner
authors.forename: David M
authors.initials: DM
authors.lastname: Alvarado
authors.forename: Lydia
authors.initials: L
authors.lastname: Burgert
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Gitlin
authors.forename: Christina A
authors.initials: CA
authors.lastname: Gurnett
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Goldsmith
mesh_terms: D000818:Animals; D018389:Codon, Nonsense; D004195:Disease Models, Animal; D016368:Frameshift Mutation; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012600:Scoliosis / Q000196:embryology* / Q000235:genetics; D013131:Spine / Q000196:embryology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018389:Codon, Nonsense; D029961:Zebrafish Proteins; D016547:Kinesins
keywords: Danio rerio; kinesin; scoliosis