Mice reveal 38 new genes involved in hearing loss

Molecular pathways revealed could identify potential drug targets for restoring hearing

Mice reveal 38 new genes involved in hearing loss

Mice reveal 38 new genes involved in hearing loss
Extensive loss of outer hair cell (OHC) hair bundles [coloured pink] revealed by scanning electron microscope (on the left), resulting in impaired hearing. Image credit: Ingham et al. (2019) PLOS Biology DOI: 10.1371/journal.pbio.3000194

Multiple new genes involved in hearing loss have been revealed in a huge study of mouse mutants by researchers from the Wellcome Sanger Institute and King’s College London, and colleagues. The new genes reveal the metabolic pathways and regulatory processes involved in hearing.

The study, published today (April 11) in the open-access journal PLOS Biology, helps to understand the underlying biology of deafness, and also provides a rich source of therapeutic targets for the restoration of hearing.

Progressive hearing loss with age is extremely common in the population, leading to difficulties in understanding speech, increased social isolation and associated depression. It can often be inherited, but so far very little is known about the molecular pathways leading to hearing loss, hampering the development of treatments.

To identify new molecules involved in hearing loss, the researchers took a genetic approach and created 1,211 new mouse mutants. They screened each of these mice using a sensitive electrophysiological test, the auditory brainstem response, to find out how good their hearing was. 

This large-scale screen of targeted mouse mutants identified 38 genes involved in hearing loss in the mice, which had not been previously suspected to be involved in hearing.

The researchers also analysed human DNA data* to ask if any of these 38 genes discovered in mice were associated with human adult-onset hearing loss. They found 11 of these 38 genes were significantly associated with hearing ability in the UK population. Furthermore one gene, SPNS2, was associated with childhood deafness.

Some of these genes revealed molecular pathways that may be useful targets for drug development.

“This is the first time that a study of this scale has looked at levels of hearing and different types of hearing loss in mouse mutants and shows the power of large genetic screens. Only a handful of genes have previously been linked specifically to age-related hearing loss in adults, now our study adds many more potential new genes to follow up.”

Dr Chris Lelliott, an author from the Wellcome Sanger Institute

Further analysis of the genes identified, and the many different mechanisms within the ear that were revealed by the mutations, suggested that hearing loss is an extremely varied disorder and may involve as many as 1,000 genes.

“This study is giving a huge insight into the complicated biology of hearing loss, and shows that because of all the different genes and pathways found, there won’t be a single ‘magic bullet’ to stop all age-related deafness. This emphasises the value of mouse studies for identifying genes and mechanisms underlying complex processes such as hearing.”

Dr Selina Pearson, from the Wellcome Sanger Institute

The study findings suggest that therapies may need to be directed at common molecular pathways involved in deafness rather than individual genes or mutations.

“Several of these new mouse mutant lines showed normal development of hearing followed by later deterioration, suggesting the genes involved are good candidates for human age-related hearing loss. Our next step is to find out if we can influence the molecular pathways involved to slow down or stop the progression of hearing loss.”

Professor Karen Steel, senior author on the paper from the Wellcome Sanger Institute and King’s College London

Notes to Editors

Ingham NJ, Pearson SA, Vancollie VE, Rook V, Lewis MA, Chen J, et al. (2019) Mouse screen reveals multiple new genes underlying mouse and human hearing loss. PLOS Biology. DOI: 10.1371/journal.pbio.3000194

*This work used openly accessible data and samples generated by the 1958 Birth Cohort https://www.metadac.ac.uk/1958bc/


This work was supported by Wellcome, the Medical Research Council, European Commission, Action on Hearing Loss, the Haigh Fellowship in age related deafness, and Deafness Research UK.

Selected Websites
Cause of selective male deafness discoveredSanger ScienceCause of selective male deafness discovered
13 Feb 2013: For one family at least, selective male deafness is true. A team at the Sanger Institute has discovered a mutation on the male-only Y chromosome that causes adult deafness, Yali Xue re…

A Cornucopia of Candidates for DeafnessSanger ScienceA Cornucopia of Candidates for Deafness
25 Sept 2012: Morag Lewis talks about a review she has had published in Cell. The study looked at genes and investigated how the loss of those genes affected the fly. Losing some of the genes resul…

Why use the mouse in research?FactsWhy use the mouse in research?
Humans and mice share many common genetic features and by examining the physiology, anatomy and metabolism of a mouse, scientists can gain a valuable insight into how humans function. 

Of mice and menStoriesOf mice and men
The mouse is closely related to humans with a striking similarity to us in terms of anatomy, physiology and genetics. This makes the mouse an extremely useful model organism. 

Should animals be used in research?DebatesShould animals be used in research?
Animals, from the fruit fly to the mouse, are widely used in scientific research. They are crucial for allowing scientists to learn more about human biology and health, and for developing new medicines. 

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