PUBLICATION
SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation
- Authors
- Xu, H., Dugué, G.P., Cantaut-Belarif, Y., Lejeune, F.X., Gupta, S., Wyart, C., Lehtinen, M.K.
- ID
- ZDB-PUB-231205-5
- Date
- 2023
- Source
- Fluids and barriers of the CNS 20: 8989 (Journal)
- Registered Authors
- Wyart, Claire
- Keywords
- Cerebrospinal fluid, Reissner’s fiber, SCO-spondin/SSPO, Spinal cord, Spine deformities, Subcommissural organ (SCO), Ventricular volume
- MeSH Terms
-
- Animals
- Cell Adhesion Molecules, Neuronal*/metabolism
- Cerebral Ventricles*/metabolism
- Mice
- Spinal Cord/metabolism
- Zebrafish*/metabolism
- PubMed
- 38049798 Full text @ Fluids Barriers CNS
Citation
Xu, H., Dugué, G.P., Cantaut-Belarif, Y., Lejeune, F.X., Gupta, S., Wyart, C., Lehtinen, M.K. (2023) SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation. Fluids and barriers of the CNS. 20:8989.
Abstract
Reissner's fiber (RF) is an extracellular polymer comprising the large monomeric protein SCO-spondin (SSPO) secreted by the subcommissural organ (SCO) that extends through cerebrospinal fluid (CSF)-filled ventricles into the central canal of the spinal cord. In zebrafish, RF and CSF-contacting neurons (CSF-cNs) form an axial sensory system that detects spinal curvature, instructs morphogenesis of the body axis, and enables proper alignment of the spine. In mammalian models, RF has been implicated in CSF circulation. However, challenges in manipulating Sspo, an exceptionally large gene of 15,719 nucleotides, with traditional approaches has limited progress. Here, we generated a Sspo knockout mouse model using CRISPR/Cas9-mediated genome-editing. Sspo knockout mice lacked RF-positive material in the SCO and fibrillar condensates in the brain ventricles. Remarkably, Sspo knockout brain ventricle sizes were reduced compared to littermate controls. Minor defects in thoracic spine curvature were detected in Sspo knockouts, which did not alter basic motor behaviors tested. Altogether, our work in mouse demonstrates that SSPO and RF regulate ventricle size during development but only moderately impact spine geometry.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping