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

Ernest, S., Rauch, G.J., Haffter, P., Geisler, R., Petit, C., and Nicolson, T.
Human molecular genetics   9(14): 2189-2196 (Journal)
Registered Authors
Ernest, Sylvain, Geisler, Robert, Haffter, Pascal, Nicolson, Teresa, Petit, Christine, Rauch, Gerd-Jörg
MeSH Terms
  • Alleles
  • Animals
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA, Complementary/metabolism
  • DNA-Binding Proteins/biosynthesis
  • DNA-Binding Proteins/genetics*
  • Dyneins
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/ultrastructure
  • Hearing Loss, Sensorineural/genetics*
  • In Situ Hybridization
  • Mice
  • Microscopy, Electron
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation, Missense*
  • Myosins/biosynthesis
  • Myosins/genetics*
  • Phenotype
  • Physical Chromosome Mapping
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Messenger/metabolism
  • Time Factors
  • Transposases
  • Zebrafish
10958658 Full text @ Hum. Mol. Genet.
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.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes