Kinesin family member 6 (kif6) is necessary for spine development in zebrafish. Issue 12 (20th October 2014)

• Record Type: Journal Article
• Authors: Buchan, Jillian G.; Gray, Ryan S.; Gansner, John M.; Alvarado, David M.; Burgert, Lydia; Gitlin, Jonathan D.; Gurnett, Christina A.; Goldsmith, Matthew I.
• Is Part Of: Developmental dynamics. Volume 243:Issue 12(2014:Dec.)
• Page Start: 1646
• Page End: 1657
• Publication Date: 2014-10-20
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24208
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <underline>Background</underline>: 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. <underline>Results:</underline> We performed a forward mutagenesis screen in zebrafish to identify new models for idiopathic scoliosis. We isolated a recessive zebrafish mutant, called <italic>skolios</italic>, which develops isolated spinal curvature that arises independent of vertebral malformations. Using meiotic mapping and whole genome sequencing, we identified a nonsense mutation in <italic>kinesin family member 6</italic> (<italic>kif6</italic><sup>gw326</sup>) unique to <italic>skolios</italic> mutants. Three additional <italic>kif6</italic> frameshift alleles (gw327, gw328, gw329) were generated with transcription activator‐like effector nucleases (TALENs). Zebrafish homozygous or compound heterozygous for <italic>kif6</italic> frameshift mutations developed a scoliosis phenotype indistinguishable from <italic>skolios</italic> mutants, confirming that <italic>skolios</italic> is caused by the loss of <italic>kif6</italic>. Although <italic>kif6</italic> may play a role in cilia, no evidence for cilia dysfunction was seen in <italic>kif6</italic><sup>gw326</sup> mutants. <underline>Conclusions:</underline> Overall, these findings demonstrate a novel role for <italic>kif6</italic> in spinal development and identify a new candidate gene for human idiopathic scoliosis. <italic>Developmental Dynamics 243:1646–1657, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </abstract>