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A Chromosome 17 Locus Engenders Frequency-Specific Non-Progressive Hearing Loss that Contributes to Age-Related Hearing Loss in Mice

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Abstract

The 129S6/SvEvTac (129S6) inbred mouse is known for its resistance to noise-induced hearing loss (NIHL). However, less is understood of its unique age-related hearing loss (AHL) phenotype and its potential relationship with the resistance to NIHL. Here, we studied the physiological characteristics of hearing loss in 129S6 and asked if noise resistance (NR) and AHL are genetically linked to the same chromosomal region. We used auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to examine hearing sensitivity between 1 and 13 months of age of recombinant-inbred (congenic) mice with an NR phenotype. We identified a region of proximal chromosome (Chr) 17 (D17Mit143-D17Mit100) that contributes to a sensory, non-progressive hearing loss (NPHL) affecting exclusively the high-frequencies (>24 kHz) and maps to the nr1 locus on Chr 17. ABR experiments showed that 129S6 and CBA/CaJ F1 (CBACa) hybrid mice exhibit normal hearing, indicating that the hearing loss in 129S6 mice is inherited recessively. An allelic complementation test between the 129S6 and 101/H (101H) strains did not rescue hearing loss, suggesting genetic allelism between the nphl and phl1 loci of these strains, respectively. The hybrids had a milder hearing loss than either parental strain, which indicate a possible interaction with other genes in the mouse background or a digenic interaction between different genes that reside in the same genomic region. Our study defines a locus for nphl on Chr 17 affecting frequencies greater than 24 kHz.

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Acknowledgments

The authors would like to thank Jennifer Larson for her constructive criticisms in the preparation of the manuscript, Sharon G. Kujawa for her support and discussion of techniques and results, Tina Chan for the ABR threshold verification, and the members of the Tempel laboratory for their technical support and constructive discussion of the research. This work was supported by grants from DoD W81XWH-11-2-0037 (BLT) and NIH R01DC02739 (BLT), R01DC06305 (BLT), P30DC04661 (BLT), T32DC000033 (BP), T32GM007108 (BP), and T32DC000018 (BP).

Conflict of Interest

The authors would like to declare no commercial or other conflict of interests.

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Authors and Affiliations

  1. The Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA, 98195, USA

    Braulio Peguero & Bruce L Tempel

  2. The Graduate Program in Neuroscience, University of Washington, Box 357270, Seattle, WA, 98195, USA

    Braulio Peguero & Bruce L Tempel

  3. Department of Pharmacology, University of Washington, Box 357280, Seattle, WA, 98195, USA

    Bruce L Tempel

  4. Department of Otolaryngology-HNS, University of Washington, Box 356515, Seattle, WA, 98195, USA

    Bruce L Tempel

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  1. Braulio Peguero
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Correspondence to Bruce L Tempel.

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Peguero, B., Tempel, B.L. A Chromosome 17 Locus Engenders Frequency-Specific Non-Progressive Hearing Loss that Contributes to Age-Related Hearing Loss in Mice. JARO 16, 459–471 (2015). https://doi.org/10.1007/s10162-015-0519-7

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  • DOI: https://doi.org/10.1007/s10162-015-0519-7

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