A mouse model for human hearing loss DFNB30 due to loss of function of myosin IIIA

Vanessa L. Walsh; Dorith Raviv; Amiel A. Dror; Hashem Shahin; Tom Walsh; Moien N. Kanaan; Karen B. Avraham; Mary Claire King

doi:10.1007/s00335-010-9310-6

A mouse model for human hearing loss DFNB30 due to loss of function of myosin IIIA

Vanessa L. Walsh, Dorith Raviv, Amiel A. Dror, Hashem Shahin, Tom Walsh, Moien N. Kanaan, Karen B. Avraham, Mary Claire King

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

The motor protein myosin IIIA is critical for maintenance of normal hearing. Homozygosity and compound heterozygosity for loss-of-function mutations in MYO3A, which encodes myosin IIIA, are responsible for inherited human progressive hearing loss DFNB30. To further evaluate this hearing loss, we constructed a mouse model, Myo3aKI/KI, that harbors the mutation equivalent to the nonsense allele responsible for the most severe human phenotype. Myo3aKI/KI mice were compared to their wildtype littermates. Myosin IIIA, with a unique N-terminal kinase domain and a C-terminal actin-binding domain, localizes to the tips of stereocilia in wild-type mice but is absent in the mutant. The phenotype of the Myo3aKI/KI mouse parallels the phenotype of human DFNB30. Hearing loss, as measured by auditory brainstem response, is reduced and progresses significantly with age. Vestibular function is normal. Outer hair cells of Myo3aKI/KI mice degenerate with age in a pattern consistent with their progressive hearing loss.

Original language	English
Pages (from-to)	170-177
Number of pages	8
Journal	Mammalian Genome
Volume	22
Issue number	3-4
DOIs	https://doi.org/10.1007/s00335-010-9310-6
State	Published - Apr 2011
Externally published	Yes

Bibliographical note

Funding Information:
We thank members of Family N for their continuous participation in our study. This work was supported by NIH grant R01DC005641 from the National Institute of Deafness and Communication Disorders. We thank Mario Capecchi for the ACN cassette; Richard Palmiter for plasmid p4317G9; Carlos Gordon for vestibular testing; and Yehoash Raphael, Edwin Rubel, Carol Ware, Carol Robbins, Bob Hunter, and Glenn MacDonald for technical help and advice.

Funding

We thank members of Family N for their continuous participation in our study. This work was supported by NIH grant R01DC005641 from the National Institute of Deafness and Communication Disorders. We thank Mario Capecchi for the ACN cassette; Richard Palmiter for plasmid p4317G9; Carlos Gordon for vestibular testing; and Yehoash Raphael, Edwin Rubel, Carol Ware, Carol Robbins, Bob Hunter, and Glenn MacDonald for technical help and advice.

Funders	Funder number
National Institutes of Health
National Institute on Deafness and Other Communication Disorders	R01DC005641

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title = "A mouse model for human hearing loss DFNB30 due to loss of function of myosin IIIA",

abstract = "The motor protein myosin IIIA is critical for maintenance of normal hearing. Homozygosity and compound heterozygosity for loss-of-function mutations in MYO3A, which encodes myosin IIIA, are responsible for inherited human progressive hearing loss DFNB30. To further evaluate this hearing loss, we constructed a mouse model, Myo3aKI/KI, that harbors the mutation equivalent to the nonsense allele responsible for the most severe human phenotype. Myo3aKI/KI mice were compared to their wildtype littermates. Myosin IIIA, with a unique N-terminal kinase domain and a C-terminal actin-binding domain, localizes to the tips of stereocilia in wild-type mice but is absent in the mutant. The phenotype of the Myo3aKI/KI mouse parallels the phenotype of human DFNB30. Hearing loss, as measured by auditory brainstem response, is reduced and progresses significantly with age. Vestibular function is normal. Outer hair cells of Myo3aKI/KI mice degenerate with age in a pattern consistent with their progressive hearing loss.",

author = "Walsh, {Vanessa L.} and Dorith Raviv and Dror, {Amiel A.} and Hashem Shahin and Tom Walsh and Kanaan, {Moien N.} and Avraham, {Karen B.} and King, {Mary Claire}",

note = "Funding Information: We thank members of Family N for their continuous participation in our study. This work was supported by NIH grant R01DC005641 from the National Institute of Deafness and Communication Disorders. We thank Mario Capecchi for the ACN cassette; Richard Palmiter for plasmid p4317G9; Carlos Gordon for vestibular testing; and Yehoash Raphael, Edwin Rubel, Carol Ware, Carol Robbins, Bob Hunter, and Glenn MacDonald for technical help and advice.",

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A mouse model for human hearing loss DFNB30 due to loss of function of myosin IIIA

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