PUBLICATION
Otoferlin Deficiency In Zebrafish Results In Defects In Balance And Hearing: Rescue Of The Balance And Hearing Phenotype With Full-length And Truncated Forms Of Mouse Otoferlin
- Authors
- Chatterjee, P., Padmanarayana, M., Abdullah, N., Holman, C.L., LaDu, J., Tanguay, R.L., Johnson, C.P.
- ID
- ZDB-PUB-150115-17
- Date
- 2015
- Source
- Molecular and cellular biology 35(6): 1043-54 (Journal)
- Registered Authors
- Tanguay, Robyn L.
- Keywords
- none
- MeSH Terms
-
- Animals
- Deafness/metabolism*
- Deafness/physiopathology
- Exocytosis/physiology
- Hair Cells, Auditory/metabolism*
- Hair Cells, Auditory/physiology
- Hearing/physiology*
- Humans
- Locomotion/physiology
- Membrane Proteins/metabolism*
- Mesencephalon/metabolism
- Mice
- Phenotype
- Protein Structure, Tertiary
- Synapses/metabolism
- Zebrafish/metabolism*
- Zebrafish/physiology
- PubMed
- 25582200 Full text @ Mol. Cell. Biol.
Citation
Chatterjee, P., Padmanarayana, M., Abdullah, N., Holman, C.L., LaDu, J., Tanguay, R.L., Johnson, C.P. (2015) Otoferlin Deficiency In Zebrafish Results In Defects In Balance And Hearing: Rescue Of The Balance And Hearing Phenotype With Full-length And Truncated Forms Of Mouse Otoferlin. Molecular and cellular biology. 35(6):1043-54.
Abstract
Sensory hair cells convert mechanical motion into chemical signals. Otoferlin, a six-C2 domain transmembrane protein linked to deafness in humans, is hypothesized to play a role in exocytosis at hair cell ribbon synapses. To date however, otoferlin has been studied almost exclusively in mouse models, and no rescue experiments have been reported. Here we describe the phenotype associated with morpholino induced otoferlin knockdown in zebrafish, and report the results of rescue experiments conducted with full length and truncated forms of otoferlin. We find that expression of otoferlin occurs early in development, and is restricted to hair cells and the midbrain. Immunofluorescence microscopy reveals localization to both apical and basolateral regions of hair cells. Knockdown of otoferlin results in hearing and balance defects, as well as locomotion deficiencies. Further, otoferlin morphants had uninflated swim bladders. Rescue experiments conducted with mouse otoferlin restored hearing, balance and inflation of the swim bladder. Remarkably, truncated forms of otoferlin retaining the C-terminal C2F domain also rescued the otoferlin knockdown phenotype, while the individual N-terminal C2A domain did not. We conclude that otoferlin plays an evolutionarily conserved role in vertebrate hearing, and that truncated forms of otoferlin can rescue hearing and balance.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping