PUBLICATION
Tmc proteins are essential for zebrafish hearing where Tmc1 is not obligatory
- Authors
- Chen, Z., Zhu, S., Kindig, K., Wang, S., Chou, S.W., Davis, R.W., Dercoli, M.R., Weaver, H., Stepanyan, R., McDermott, B.M.
- ID
- ZDB-PUB-200403-58
- Date
- 2020
- Source
- Human molecular genetics 29(12): 2004-2021 (Journal)
- Registered Authors
- Chou, Shih-wei, Davis, Robin Woods, McDermott Jr., Brian M., Zhu, Shaoyuan (Sara)
- Keywords
- none
- MeSH Terms
-
- Animals
- Deafness/genetics
- Deafness/pathology
- Hair Cells, Auditory/metabolism
- Hair Cells, Auditory/pathology
- Hair Cells, Auditory, Inner/metabolism
- Hair Cells, Auditory, Inner/pathology
- Hearing/genetics*
- Hearing Loss, Sensorineural/genetics*
- Hearing Loss, Sensorineural/pathology
- Humans
- Mechanotransduction, Cellular/genetics
- Membrane Proteins/genetics*
- Mice
- Mutation/genetics
- Stereocilia/genetics
- Stereocilia/pathology
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- PubMed
- 32167554 Full text @ Hum. Mol. Genet.
Citation
Chen, Z., Zhu, S., Kindig, K., Wang, S., Chou, S.W., Davis, R.W., Dercoli, M.R., Weaver, H., Stepanyan, R., McDermott, B.M. (2020) Tmc proteins are essential for zebrafish hearing where Tmc1 is not obligatory. Human molecular genetics. 29(12):2004-2021.
Abstract
Perception of sound is initiated by mechanically-gated ion channels at the tips of stereocilia. Mature mammalian auditory hair cells require transmembrane channel-like 1 (TMC1) for mechanotransduction and mutations of the cognate genetic sequences result in dominant or recessive heritable deafness forms in humans and mice. In contrast, zebrafish lateral line hair cells, which detect water motion, require Tmc2a and Tmc2b. Here, we use standard and multiplex genome editing in conjunction with functional and behavioral assays to determine the reliance of zebrafish hearing and vestibular organs on Tmc proteins. Surprisingly, our approach using multiple mutant alleles demonstrates that hearing in zebrafish is not dependent on Tmc1, nor is it fully dependent on Tmc2a and Tmc2b. Hearing however is absent in triple-knockout zebrafish that lack Tmc1, Tmc2a, and Tmc2b. These outcomes reveal a striking resemblance of Tmc protein reliance in the vestibular sensory epithelia of mammals to the maculae of zebrafish. Moreover, our findings disclose a logic of Tmc use where hearing depends on a complement of Tmc proteins beyond those employed to sense water motion.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping