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Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice

Gene Therapy volume 18, pages 560–568 (2011)Cite this article

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Abstract

Apoptosis is responsible for cochlear cell death induced by noise. Here, we show that transgenic (TG) mice that overexpress X-linked inhibitor of apoptosis protein (XIAP) under control of the ubiquitin promoter display reduced hearing loss and cochlear damage induced by acoustic overstimulation (125 dB sound pressure level, 6 h) compared with wild-type (WT) littermates. Hearing status was evaluated using the auditory brainstem response (ABR), whereas cochlear damage was assessed by counts of surviving hair cells (HCs) and spiral ganglion neurons (SGNs) as well as their fibers to HCs. Significantly smaller threshold shifts were found for TG mice than WT littermates. Correspondingly, the TG mice also showed a reduced loss of HCs, SGNs and their fibers to HCs. HC loss was limited to the basal end of the cochlea that detects high frequency sound. In contrast, the ABRs demonstrated a loss of hearing sensitivity across the entire frequency range tested (2–32 kHz) indicating that the hearing loss could not be fully attributed to HC loss alone. The TG mice displayed superior hearing sensitivity over this whole range, suggesting that XIAP overexpression reduces noise-induced hearing loss not only by protecting HCs but also other components of the cochlea.

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Abbreviations

ABR:

Auditory Brainstem Response

HC:

Hair Cell

IAP:

Inhibitor of Apoptosis Protein

IHC:

Inner Hair Cell

OHC:

Outer Hair Cell

NIHL:

Noise-Induced Hearing Loss

OC:

Organ of Corti

SGN:

Spiral Ganglion Neuron

TG:

Transgenic

ub-XIAP:

Ubiquitous X-linked Inhibitor of Apoptosis Protein

WT:

Wild Type

XIAP:

X-linked Inhibitor of Apoptosis Protein

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Acknowledgements

This thesis project was supported by the research grant of Canadian Institute of Health Research (MOP79452), the Program of Shanghai Subject Chief Scientist (08XD1403100) and the Special Program for Key Basic Research of the Ministry of Science and Technology of China (2009CB526504). We thank Dr Kiefte for his assistance in data analysis.

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Authors and Affiliations

  1. School of Human Communication Disorder, Dalhousie University, Halifax, Nova Scotia, Canada

    J Wang, N Tymczyszyn, Z Yu & M Bance

  2. Department of Physiology & Pharmacology, Southeast University, Nanjing, China

    J Wang

  3. The Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China

    S Yin

  4. Division of Otolaryngology, Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada

    M Bance

  5. Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada

    M Bance

  6. Departments of Psychiatry and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada

    G S Robertson

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Correspondence to J Wang or S Yin.

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Wang, J., Tymczyszyn, N., Yu, Z. et al. Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice. Gene Ther 18, 560–568 (2011). https://doi.org/10.1038/gt.2010.172

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