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What can a malformed jaw in zebrafish tell us about hearing loss in humans? A lot, says a new study published in Scientific Reports.

In a fantastic example of evolutionary biology, the structures that make up the fish jaw correlate to three tiny bones that make up the mammalian ear. This led researchers to wonder if genetic changes that cause jaw malformation would also match up to the genetic changes that cause hearing defects in mice and humans.

"One of the most fascinating evolutionary stories is the transition of the ancestral fish jaw bones into the tiny middle ear bones, which occurred as vertebrates came out of the water and starting hearing in air. Reflecting their common evolutionary origin, what we are finding is that genetic mutations that affect the fish jaw bones similarly affect the middle ear bones in mammals such as ourselves. This evolutionary homology has allowed us to use zebrafish to find genes important for forming the human middle ear," Gage Crump, one of the study's authors, explained to ALN.

For the current study, researchers at the University of Southern California and the Children's Hospital of Los Angeles studied the two genes--JAG1 and NOTCH2. These genes are mutated in most patients wih Alagille Syndrome, which causes hearing loss and liver, eye, heart, and skeletal defects.

Researchers introduced genetic mutations seen in jaw malformations in zebrafish into laboratory mice. This resulted in defects in both the incus and stapes, two of the three bones in the rodents ear. Hearing loss also occurred.

Interestingly, the correlation between zebrafish jaws and hearing also translated to human patients.

"In some people with JAGGED1 mutations, we also found that the stapes and incus bones, as well as other middle ear structures, were abnormal, again as predicted by our zebrafish phenotype. This finding is significant for patients, as there exist surgical options for correcting these middle ear defects and partially restoring hearing," Gage added.

"The published study involved an extensive collaboration between basic researchers working in zebrafish and mice with clinicians who specialize in pediatric genetics, radiology, and audiology. By bringing these basic researchers and clinicians together, we were able to rapidly take basic knowledge learned in model organisms and arrive at conclusions that are already having an impact for patients' lives."

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