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gom1 Mutant Mice as a Model of Otitis Media

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Abstract

Otitis media (OM) disease is a common cause of hearing loss that is primarily the result of middle ear infection. At present, our understanding of the mechanisms leading to OM is limited due to the lack of animal models of OM with effusion (OME). Here, we report that the mice with genetic otitis media one (gom1) mutants are prone to OM. gom1 Mice were produced by the N-ethyl-N-nitrosourea (ENU) mutagenesis program as an animal model to study OM. These mice demonstrate many common features of OM, such as middle ear effusion and hearing impairment. We revealed that gom1 mice display various signs of middle ear and inner ear dysfunctions, including elevated thresholds of auditory-evoked brainstem response (ABR) and lack of cochlear microphonic responses. Decreased compliance in tympanometry measurements indicates tympanic membrane and ossicular chain malfunction. We confirmed through histological examinations of middle ear structures that 34/34 (100 %) of the mutant mice suffered from severe OME. While individual ears had different levels of effusion and inflammatory cells in the middle ear cavity, all had thickened middle ear mucosa and submucosa compared to control mice (B6). Moreover, the mutant mice displayed cochlear hair cell loss. These observations also suggested the craniofacial abnormalities in the gom1 mouse model. Together, these results indicate that gom1 mice could be valuable for investigating the genetic contribution to the development of middle ear disease.

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Acknowledgements

We thank Shengli Li and Jiangping Zhang for assistance. We thank Dr. Chuan-ming Li, from NIDCD and Dr. Ruili Xie from Ohio State University for their advice on Statistics.

Funding

This work was supported by the National Institutes of Health (R01DC015111 and R21DC005846), the National Natural Science Foundation of China (81530030, 81500797, 81873697 and 81700902), and the Taishan Scholars Foundation.

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Authors and Affiliations

  1. Department of Otolaryngology, Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China

    Tihua Zheng, Yan Zhang & Qing Yin Zheng

  2. Department of Otolaryngology, Case Western Reserve University, Cleveland, OH, 44106, USA

    Wenyi Huang, Heping Yu, Peter Song, Joseph Jaster & Qing Yin Zheng

  3. Department of Communicative Disorders and Sciences, Center for Hearing and Deafness, State University of New York at Buffalo, Buffalo, USA

    Bo Hua Hu

  4. Jackson Laboratory, Bar Harbor, USA

    Christopher M. McCarty

  5. Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA

    Lu Lu

  6. Department of Biological Sciences, Case Western Reserve University School of Dental Medicine, 10900 Euclid Ave, Cleveland, OH, USA

    Ge Jin

Authors
  1. Tihua Zheng
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  2. Wenyi Huang
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  3. Heping Yu
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  4. Bo Hua Hu
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  5. Peter Song
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  6. Christopher M. McCarty
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  7. Lu Lu
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  8. Joseph Jaster
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  9. Ge Jin
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  10. Yan Zhang
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  11. Qing Yin Zheng
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Contributions

All the authors were involved with the conception and design of the manuscript, manuscript writing, and final approval of the manuscript.

Corresponding authors

Correspondence to Yan Zhang or Qing Yin Zheng.

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The authors declare no competing interests.

Contribution to the Field

Many children experience OM, a leading cause of hearing loss in the pediatric population. OM is characterized by middle ear effusion. The Jackson Laboratory has established the Neuroscience Mutagenesis Facility to produce novel neurological mouse models for exploring basic neurobiological mechanisms and diseases. At present, a few mouse models have been identified for research of OM. However, the incidence of OM can differ among these mouse strains. Our study reveals that gom1 mice are a valuable ENU mouse model for studying OM. In contrast to previously reported ENU models, almost 100 % of gom1 mice demonstrate OM. These mice display the phenotypes of OM that mimic the clinically observed signs of OM in humans, such as fluid in the middle ear cavity and hearing loss. This study provides groundwork for future studies aiming at a better understanding of molecular mechanisms underlying the increased susceptibility of mutant mice to middle ear infection, which, in turn, is important for an understanding of individual variation in human vulnerability to OM.

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Tihua Zheng, Wenyi Huang, and Heping Yu are co-first authors.

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Zheng, T., Huang, W., Yu, H. et al. gom1 Mutant Mice as a Model of Otitis Media. JARO 23, 213–223 (2022). https://doi.org/10.1007/s10162-022-00838-2

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  • DOI: https://doi.org/10.1007/s10162-022-00838-2

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