Scientists believe that a zebrafish with a malformed jaw offers revealing findings for colleagues in radiology, audiology and genetics
BY Cristy Lytal
Can a fish with a malformed jaw tell us something about hearing loss in mice and humans? The answer is yes, according to new findings in Scientific Reports.
In an evolutional twist, the structures supporting the jaws of ancestral fish gave rise to three tiny bones in the mammalian middle ear — the malleus, incus and the stapes — which transmit sound vibrations. So the researchers believe that if a genetic change causes a jaw malformation in a fish, an equivalent genetic change could trigger hearing defects in mice and humans.
To test that idea, first author and PhD student Camilla Teng brought together colleagues in the USC Stem Cell laboratories of Gage Crump, Rob Maxson and Neil Segil with clinical experts in radiology, audiology and genetics at the Keck School of Medicine of USC and Children’s Hospital Los Angeles.
Together, they studied two genes that are mutated in most patients with Alagille syndrome, a genetic condition that results in various symptoms in different parts of the body, including the liver. In nearly half of patients, the syndrome involves hearing loss in addition to liver, eye heart and skeletal defects. While some of this is hearing loss resulting from deficits in the sensory cells of the inner ear, the researchers also wondered about conductive hearing loss, which involves structural components of the middle ear such as the vibrating bones.
Tests will tell
Knowing that the equivalent genetic mutations caused jaw malformations in zebrafish, the researchers introduced the mutations into mice and observed defects in both the incus and stapes bones along with corresponding hearing loss.
Later they performed hearing tests on 44 patients. As predicted by their findings in zebrafish and mice, conductive hearing loss was the most common type, affecting nearly one-third of all ears.
The study highlights a mostly overlooked phenotype of Alagille Syndrome, according to Teng. “If patients are aware of possible conductive hearing loss earlier in life, they can more promptly seek medical aids for an improved quality of life,” she said.
Additional co-authors include Hai-Yun Yen, Lindsey Barske, Juan Llamas and John Go from the Keck School of Medicine and Bea Smith and Pedro A. Sanchez-Lara from Children’s Hospital Los Angeles.
Fifty percent of the project was supported by $400,000 of federal funding from the National Institutes of Health (grants/fellowship DE018405, DE024031, DE016320 and DC009975). The other 50 percent of private funding came from the March of Dimes.
University of Southern California