Eya4-deficient mice are a model for heritable otitis media
Frederic F.S. Depreux, Keith Darrow, David A. Conner, Roland D. Eavey, M. Charles Liberman, Christine E. Seidman, J.G. Seidman
Frederic F.S. Depreux, Keith Darrow, David A. Conner, Roland D. Eavey, M. Charles Liberman, Christine E. Seidman, J.G. Seidman
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Research Article

Eya4-deficient mice are a model for heritable otitis media

Abstract

Otitis media is an extremely common pediatric inflammation of the middle ear that often causes pain and diminishes hearing. Vulnerability to otitis media is due to eustachian tube dysfunction as well as other poorly understood factors, including genetic susceptibility. As EYA4 mutations cause sensorineural hearing loss in humans, we produced and characterized Eya4-deficient (Eya4–/–) mice, which had severe hearing deficits. In addition, all Eya4–/– mice developed otitis media with effusion. Anatomic studies revealed abnormal middle ear cavity and eustachian tube dysmorphology; thus, Eya4 regulation is critical for the development and function of these structures. We suggest that some human otitis media susceptibility reflects underlying genetic predisposition in genes like EYA4 that regulate middle ear and eustachian tube anatomy.

Authors

Frederic F.S. Depreux, Keith Darrow, David A. Conner, Roland D. Eavey, M. Charles Liberman, Christine E. Seidman, J.G. Seidman

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Figure 1

Eya4-targeting strategy.

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Eya4-targeting strategy. (A) A Neo and Zeo cassette fla...
(A) A Neo and Zeo cassette flanked by loxP sites (black triangles) was inserted into Eya4 exons 8–10 by homologous recombination in bacteria. The mutant allele was introduced into ES cells using standard homologous recombination techniques (see Methods). (B) PCR analyses of wild-type (+/+), homozygous Eya4–/– (–/–), and heterozygous Eya4+/– (+/–) genotypes. Primers intron 7F (I7F), exon 8R (E8R), and NeoR demonstrated the presence of wild-type (516 bp) and mutant (446 bp) alleles. (C) RT-PCR of cardiac cDNA using external forward primer 4F and internal reverse primer 9R identified a single 469-bp product in wild-type (+/+) and heterozygous Eya4+/– (+/–) but not Eya4–/– (–/–) mice.