First Author | Liu LM | Year | 2023 |
Journal | Sci Adv | Volume | 9 |
Issue | 6 | Pages | eadf4144 |
PubMed ID | 36753545 | Mgi Jnum | J:339757 |
Mgi Id | MGI:7433792 | Doi | 10.1126/sciadv.adf4144 |
Citation | Liu LM, et al. (2023) Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise. Sci Adv 9(6):eadf4144 |
abstractText | 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. |