Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise

Abstract

Gap junction gene GJB2 (Cx26) mutations cause >50% of nonsyndromic hearing loss. Its recessive hetero-mutation carriers, who have no deafness, occupy ~10 to 20% of the general population. Here, we report an unexpected finding that these heterozygote carriers have hearing oversensitivity, and active cochlear amplification increased. Mouse models show that Cx26 hetero-deletion reduced endocochlear potential generation in the cochlear lateral wall and caused outer hair cell electromotor protein prestin compensatively up-regulated to increase active cochlear amplification and hearing sensitivity. The increase of active cochlear amplification also increased sensitivity to noise; exposure to daily-level noise could cause Cx26 +/− mice permanent hearing threshold shift, leading to hearing loss. This study demonstrates that Cx26 recessive heterozygous mutations are not “harmless” for hearing as previously considered and can cause hyperacusis-like hearing oversensitivity. The data also indicate that GJB2 hetero-mutation carriers are vulnerable to noise and should avoid noise exposure in daily life.

Ototoxicity of polystyrene nanoplastics in mice, HEI-OC1 cells and zebrafish

“…ABR was evoked by different frequencies of sound (clicks, 8, 16, and 32 kHz) through the closed-field speaker. As the lowest level at which a visual waveform response could be observed, the ABR threshold was defined ( Liu et al, 2023 ).…”

Prevention and treatment of noise-induced hearing loss and cochlear synapse degeneration by potassium channel blockersin vivo

“…Mice were awake in a small cage under loud-speakers in a sound-proof chamber and exposed to white-noise (95-98 dB SPL) for 2 h, one time. The sound pressure level and spectrum in the cage were measured prior to placement of the animal (Zhao et al, 2021(Zhao et al, , 2022Liu et al, 2023). For each time of noise exposure, 2-4 mice were exposed and randomly separated to treatment groups and control group to ensure age-matched control and background noise control among the experimental groups.…”

“…ABR was recorded by use of a Tucker-Davis R3 workstation with ES-1 high frequency speaker (Tucker-Davis Tech. Alachua, FL) (Zhu et al, 2013(Zhu et al, , 2015Mei et al, 2017;Zhao et al, 2022;Liu et al, 2023). ABR was recorded by stimulation with clicks in alternative polarity and tone bursts (4-40 kHz) from 80 to 10 dB SPL in a 5 dB step in a double-walled sound isolation room.…”

“…The intensity of f1 (I1) was set at 5 dB SPL higher than that of f2 (I2). The responses were averaged by 150 times (Zhu et al, 2013(Zhu et al, , 2015Zhao et al, 2022;Liu et al, 2023).…”

Cx26 heterozygous mutations: role in hyperacusis and vulnerability to noise

“…The authors also found that children who carry a single-point heterozygous mutation in the gap junction (GJ) gene Cx26 (GJB2) are susceptible to noise, which eventually leads to hearing loss (HL). 1 …”