2. Academic Validation
  3. Mouse screen reveals multiple new genes underlying mouse and human hearing loss

Mouse screen reveals multiple new genes underlying mouse and human hearing loss

  • PLoS Biol. 2019 Apr 11;17(4):e3000194. doi: 10.1371/journal.pbio.3000194.
Neil J Ingham 1 2,  Selina A Pearson 1,  Valerie E Vancollie 1,  Victoria Rook 2,  Morag A Lewis 1 2,  Jing Chen 1 2,  Annalisa Buniello 1 2,  Elisa Martelletti 2,  Lorenzo Preite 2,  Chi Chung Lam 2,  Felix D Weiss 2,  Zӧe Powis 3,  Pim Suwannarat 4,  Christopher J Lelliott 1,  Sally J Dawson 5,  Jacqueline K White 1,  Karen P Steel 1 2
Affiliations

Affiliations

  • 1 Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
  • 2 Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
  • 3 Department of Emerging Genetics Medicine, Ambry Genetics, Aliso Viejo, California, United States of America.
  • 4 Mid-Atlantic Permanente Medical Group, Rockville, Maryland, United States of America.
  • 5 UCL Ear Institute, University College London, London, United Kingdom.
PMID: 30973865 DOI: 10.1371/journal.pbio.3000194
Abstract

Adult-onset hearing loss is very common, but we know little about the underlying molecular pathogenesis impeding the development of therapies. We took a genetic approach to identify new molecules involved in hearing loss by screening a large cohort of newly generated mouse mutants using a sensitive electrophysiological test, the auditory brainstem response (ABR). We review here the findings from this screen. Thirty-eight unexpected genes associated with raised thresholds were detected from our unbiased sample of 1,211 genes tested, suggesting extreme genetic heterogeneity. A wide range of auditory pathophysiologies was found, and some mutant lines showed normal development followed by deterioration of responses, revealing new molecular pathways involved in progressive hearing loss. Several of the genes were associated with the range of hearing thresholds in the human population and one, SPNS2, was involved in childhood deafness. The new pathways required for maintenance of hearing discovered by this screen present new therapeutic opportunities.

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