Mariner is defective in myosin VIIA: a zebrafish model for human hereditary deafness

S Ernest, GJ Rauch, P Haffter, R Geisler… - Human molecular …, 2000 - academic.oup.com
S Ernest, GJ Rauch, P Haffter, R Geisler, C Petit, T Nicolson
Human molecular genetics, 2000academic.oup.com
The zebrafish (Danio rerio) possesses two mechanosensory organs believed to be
homologous to each other: the inner ear, which is responsible for the senses of audition and
equilibrium, and the lateral line organ, which is involved in the detection of water
movements. Eight zebrafish circler or auditory/vestibular mutants appear to have defects
specific to sensory hair cell function. The circler genes may therefore encode components of
the mechanotransduction apparatus and/or be the orthologous counterparts of the genes …
Abstract
The zebrafish (Danio rerio) possesses two mechanosensory organs believed to be homologous to each other: the inner ear, which is responsible for the senses of audition and equilibrium, and the lateral line organ, which is involved in the detection of water movements. Eight zebrafish circler or auditory/vestibular mutants appear to have defects specific to sensory hair cell function. The circler genes may therefore encode components of the mechanotransduction apparatus and/or be the orthologous counterparts of the genes underlying human hereditary deafness. In this report, we show that the phenotype of the circler mutant, mariner, is due to mutations in the gene encoding Myosin VIIA, an unconventional myosin which is expressed in sensory hair cells and is responsible for various types of hearing disorder in humans, namely Usher 1B syndrome, DFNB2 and DFNA11. Our analysis of the fine structure of hair bundles in the mariner mutants suggests that a missense mutation within the C-terminal FERM domain of the tail of Myosin VIIA has the potential to dissociate the two different functions of the protein in hair bundle integrity and apical endocytosis. Notably, mariner sensory hair cells display morphological and functional defects that are similar to those present in mouse shaker-1 hair cells which are defective in Myosin VIIA. Thus, this study demonstrates the striking conservation of the function of Myosin VIIA throughout vertebrate evolution and establishes mariner as the first fish model for human hereditary deafness.
Oxford University Press