Mariner is defective in myosin VIIA

A zebrafish model for human hereditary deafness

Sylvain Ernest, Gerd Jörg Rauch, Pascal Haffter, Robert Geisler, Christine Petit, Teresa Nicolson

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

The zebrafish (Danio rerio) possesses two mechano-sensory 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.

Original languageEnglish (US)
Pages (from-to)2189-2196
Number of pages8
JournalHuman Molecular Genetics
Volume9
Issue number14
StatePublished - Sep 1 2000
Externally publishedYes

Fingerprint

Deafness
Zebrafish
Myosins
Lateral Line System
Usher Syndromes
Hearing Disorders
Genes
Water Movements
Inner Ear
Missense Mutation
Endocytosis
Hearing
Vertebrates
Tail
Fishes
Phenotype
Mutation
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Ernest, S., Rauch, G. J., Haffter, P., Geisler, R., Petit, C., & Nicolson, T. (2000). Mariner is defective in myosin VIIA: A zebrafish model for human hereditary deafness. Human Molecular Genetics, 9(14), 2189-2196.

Mariner is defective in myosin VIIA : A zebrafish model for human hereditary deafness. / Ernest, Sylvain; Rauch, Gerd Jörg; Haffter, Pascal; Geisler, Robert; Petit, Christine; Nicolson, Teresa.

In: Human Molecular Genetics, Vol. 9, No. 14, 01.09.2000, p. 2189-2196.

Research output: Contribution to journalArticle

Ernest, S, Rauch, GJ, Haffter, P, Geisler, R, Petit, C & Nicolson, T 2000, 'Mariner is defective in myosin VIIA: A zebrafish model for human hereditary deafness', Human Molecular Genetics, vol. 9, no. 14, pp. 2189-2196.
Ernest S, Rauch GJ, Haffter P, Geisler R, Petit C, Nicolson T. Mariner is defective in myosin VIIA: A zebrafish model for human hereditary deafness. Human Molecular Genetics. 2000 Sep 1;9(14):2189-2196.
Ernest, Sylvain ; Rauch, Gerd Jörg ; Haffter, Pascal ; Geisler, Robert ; Petit, Christine ; Nicolson, Teresa. / Mariner is defective in myosin VIIA : A zebrafish model for human hereditary deafness. In: Human Molecular Genetics. 2000 ; Vol. 9, No. 14. pp. 2189-2196.
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