Hear This: Knockout Mice Show Genes Linked to Deafness

Fifty-two newly discovered genes that are critical for hearing have been found by testing gene-modified ‘knockout’ mice. The newly identifed genes will provide insights into the causes of hearing loss in humans. The study published Oct. 12 in Nature Communications was carried out by the International Mouse Phenotyping Consortium (IMPC), which includes the Mouse Biology Program at the University of California, Davis.

Prof. Kent Lloyd, director of the UC Davis Mouse Biology Program, in the lab. Gene-edited and “knockout” mice have become a vital tool in biomedical research. (Karin Higgins/UC Davis photo)

The consortium tested 3,006 strains of knockout mice for signs of hearing loss. Knockout mice have one gene from their genome inactivated, which helps researchers to uncover the functions of that gene. The IMPC aims to generate a knockout mouse for every gene in the mouse genome.

The hearing thresholds of the mice were assessed with rising volumes of sound at five different frequencies – mice were considered hearing impaired if they could not hear the quieter sounds for two or more frequencies.

They identified 67 genes that were associated with hearing loss, of which 52 had not been previously linked with hearing loss. The genes identified varied in how they affected hearing – effects ranged from mild to severe hearing loss or resulted in difficulties at lower or higher frequencies.

Genetic syndromes include hearing loss

In humans, there are over 400 genetic syndromes that include a hearing loss component, but most of the genes underlying hearing loss syndromes are currently unknown. The knockout mice tested so far in this study represented only about 15 percent of mouse genes, so the researchers estimate that if the entire genome is searched there will be at least 450 genes required for hearing function.

Professor Steve Brown, senior author on the paper and director of British Medical Research Council’s Harwell laboratory, said: “Importantly, the large number of hearing loss genes identified in this study demonstrates that there are many more genes involved in deafness in mouse and human genomes than we had previously realised.

“Our findings identify 52 genes that have previously not been recognised as being critical for hearing. These increase our knowledge of the many genes and molecular mechanisms required for hearing, and also provide a shortlist of new genes to investigate to discover the genetic basis of many human hearing loss syndromes. Testing these genes in people with hearing loss may help to improve diagnosis and counselling of patients.”

In the long term, these models might help identify targets for treatments for hearing loss, Brown said.

UC Davis, as part of its participation in the NIH-funded Knockout Mouse Production and Phentoyping (KOMP2) project, contributed analysis of several of these new genes that play a role in deafness, according to Professor Kent Lloyd, director of the Mouse Biology Program.

“The KOMP2 project utilizes several campus resources and expertise to conduct these studies, including the Mouse Biology Program,” Lloyd said. “The MBP has a full suite of testing platforms to reveal genetically-associated diseases and disorders.”

The program is a major resource for campus investigators using mice for discovery research, Lloyd said.

More information

Read the paper (Nature Communications)

Mouse Genome Studies Show Disease Models and Sex Differences (news release)

NIH Renews Knockout Mouse Project (news release)

UC Davis Mouse Biology Program Developing “Green” Mouse House

Adapted from a news release issued by the International Mouse Phenotyping Consortium. 

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