PUBLICATION
Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model
- Authors
- Meyer-Miner, A., Van Gennip, J.L.M., Henke, K., Harris, M.P., Ciruna, B.
- ID
- ZDB-PUB-220920-11
- Date
- 2022
- Source
- iScience 25: 105028 (Journal)
- Registered Authors
- Ciruna, Brian, Harris, Matthew, Henke, Katrin
- Keywords
- Model organism, Molecular biology experimental approach, Molecular genetics
- MeSH Terms
- none
- PubMed
- 36105588 Full text @ iScience
Citation
Meyer-Miner, A., Van Gennip, J.L.M., Henke, K., Harris, M.P., Ciruna, B. (2022) Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model. iScience. 25:105028.
Abstract
Idiopathic scoliosis (IS) refers to abnormal spinal curvatures that occur in the absence of vertebral or neuromuscular defects. IS accounts for 80% of human spinal deformity, afflicts ∼3% of children worldwide, yet pathogenic mechanisms are poorly understood. A key role for cerebrospinal fluid (CSF) homeostasis in zebrafish spine development has been identified. Specifically, defects in cilia motility of brain ependymal cells (EC), CSF flow, and/or Reissner fiber (RF) assembly are observed to induce neuroinflammation, oxidative stress, abnormal CSF-contacting neuron activity, and urotensin peptide expression, all associating with scoliosis. However, the functional relevance of these observations to IS remains unclear. Here we characterize zebrafish katnb1 mutants as a new IS model. We define essential roles for Katnb1 in motile ciliated lineages, uncouple EC cilia and RF formation defects from spinal curvature, and identify abnormal CSF flow and cell stress responses as shared pathogenic signatures associated with scoliosis across diverse zebrafish models.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping