Mouse Model Shows Auditory Impairments Similar to Patients with Fragile X, Study Says

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by Joana Carvalho |

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A mouse model of fragile X syndrome shows mild auditory impairments resembling those seen in people with the disorder, a study found.

The study, “Characterization of auditory and binaural spatial hearing in a Fragile X Syndrome mouse model,” was published in the journal eNeuro.

Fragile X is caused by mutations in the FMR1 gene, which provides instructions for making the fragile X mental retardation protein (FMRP). This protein controls the production of several other proteins in different organs, particularly the brain.

Hearing hypersensitivity is considered one of the hallmarks of fragile X, and has been associated with an imbalance of excitatory and inhibitory signals in the brain.

Excitatory and inhibitory signals work as the yin and yang of the brain, and are the basis of communication between nerve cells. While excitatory signaling spreads information by making the receiver nerve cell more likely to be activated, inhibitory signaling has the opposite effect.

The imbalance between excitatory and inhibitory signals is also thought to compromise spatial acuity — the ability to tell where a sound is coming from — and binaural hearing, which refers to the brain’s ability to combine auditory information from both ears to create a compound sound.

Previous studies in mouse models of fragile X found structural alterations in the auditory brain stem, the region of the brain responsible for spatial acuity and binaural hearing. However, it is unclear whether these brain alterations can impair both processes.

Researchers from University of Colorado Anschutz evaluated spatial acuity and binaural hearing in mice that had been genetically modified to lack both copies of the Fmr1 gene, mimicking fragile X in humans.

They evaluated the animals’ reflexive prepulse inhibition (PPI), in which a weaker stimulus (prepulse) prevents the body from reacting to a stronger startle reflex stimulus (pulse).

The investigators used a short sound coming from a different location — masked or unmasked by background noise — as a prepulse, followed by a stronger, startling noise.

Compared with healthy animals, mice lacking Fmr1 had lower PPI and took longer to react to the startling sound in all tests, regardless of the type of prepulse used, “suggesting altered timing to acoustic cues,” the researchers said. Yet the mouse model of fragile X retained the ability to identify the source of a particular sound.

“These data suggest that perhaps Fmr1 mice [lacking this gene] do not have a severe spatial hearing deficit but do show impairments in timing of responses,” the researchers said.

“However, our results are consistent with observations from human FXS [fragile X syndrome] patients, suggesting that the Fmr1 mouse model can recapitulate the human FXS condition well, at least as far as the sound localization circuit is concerned,” they said.