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A missense mutation in myosin VIIA prevents aminoglycoside accumulation in cochlear hair cells

journal contribution
posted on 2023-06-07, 22:31 authored by Guy Richardson, A Forge, Corne Kros, W Marcotti, D Becker, D S Williams, J Thorpe, J Fleming, S D Brown, K P Steel
Myosin VIIA is expressed by sensory hair cells in the inner ear and proximal tubule cells in the kidney, the two primary targets of aminoglycoside antibiotics. Using cochlear cultures prepared from early postnatal Myo7a6J mice with a missense mutation in the head region of the myosin VIIA molecule we show that this myosin is required for aminoglycoside accumulation in cochlear hair cells. Hair cells in homozygous mutant Myo7a6J cochlear cultures have disorganized hair bundles, but are otherwise morphologically normal and transduce. However, and in contrast to hair cells from heterozygous Myo7a6J cultures, the homozygous Myo7a6J hair cells do not accumulate [3H]gentamicin and do not exhibit an ototoxic response on exposure to aminoglycoside. Possible roles for myosin VIIA in the process of aminoglycoside accumulation are discussed.

History

Publication status

  • Published

Journal

Annals of the New York Academy of Sciences

Volume

884

Page range

110-124

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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