PUBLICATION
R391 human dominant mutation does not affect TubB4b localization and sensory hair cells structure in zebrafish inner ear and lateral line
- Authors
- Smaili, W., Pezet, C., Marlin, S., Ernest, S.
- ID
- ZDB-PUB-241114-58
- Date
- 2024
- Source
- Developmental Biology 517: 301-316 (Journal)
- Registered Authors
- Ernest, Sylvain
- Keywords
- TUBB4B, deafness, sensory hair cell, transgenesis, zebrafish
- MeSH Terms
-
- Hair Cells, Auditory/metabolism
- Humans
- Lateral Line System*/embryology
- Lateral Line System*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Tubulin*/genetics
- Tubulin*/metabolism
- Animals, Genetically Modified
- Animals
- Ear, Inner*/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Genes, Dominant
- Mutation/genetics
- PubMed
- 39515407 Full text @ Dev. Biol.
Citation
Smaili, W., Pezet, C., Marlin, S., Ernest, S. (2024) R391 human dominant mutation does not affect TubB4b localization and sensory hair cells structure in zebrafish inner ear and lateral line. Developmental Biology. 517:301-316.
Abstract
Heterozygous R391 TUBB4B pathogenic variations are responsible for an association of hearing loss and retinal dystrophy in human. With the goal of understanding the functions of TuBB4b and the pathogenic role of R391 variations, we characterized tubB4B in zebrafish and identified the gene regulatory elements necessary and sufficient for expression of TubB4b as in endogenous tissues. Using knock-out and transgenic approaches, we determined that R391 mutations impair neither localization of TubB4B within sensory hair cells (SHC) nor their structure, but induced to a small decrease in SHC number from anterior crista. Expression of R391 mutations in sensory hair cells has no effect on zebrafish audition, suggesting a different equilibrium between various tubulin isotypes in zebrafish possibly due to compensatory mechanisms. The careful expression analysis and transgenic tools generated in this study could help understand how recently described pathogenic variants lead to more severe clinical forms of TUBB4B-related diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping