PUBLICATION
Kinesin family member 6 (kif6) is necessary for spine development in zebrafish
- Authors
- Buchan, J.G., Gray, R.S., Gansner, J.M., Alvarado, D.M., Burgert, L., Gitlin, J.D., Gurnett, C.A., Goldsmith, M.I.
- ID
- ZDB-PUB-141007-7
- 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
- Kinesins/genetics
- Kinesins/metabolism*
- Phenotype
- Scoliosis/embryology*
- Scoliosis/genetics
- Spine/embryology*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 25283277 Full text @ Dev. Dyn.
Citation
Buchan, J.G., Gray, R.S., Gansner, J.M., Alvarado, D.M., Burgert, L., Gitlin, J.D., Gurnett, C.A., Goldsmith, M.I. (2014) Kinesin family member 6 (kif6) is necessary for spine development in zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists. 243(12):1646-57.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping