Low-intensity noise exposure takes an essential part in the mechanism of late-onset hereditary hearing loss caused by Abcc1 mutation

Clin Genet. 2024 Oct;106(4):462-475. doi: 10.1111/cge.14582. Epub 2024 Jul 1.

Abstract

With the development of the social economy, we are exposed to increasing noise in our daily lives. Our previous work found an ABCC1(NM_004996.3:c.A1769G, NP_004987.2:p.N590S) variant which cosegregated with the patients in an autosomal dominant non-syndromic hearing loss family. At present, the specific mechanism of deafness caused by ABCC1 mutation is still not clear. Using the knock-in mouse model simulating human ABCC1 mutation, we found that the occurrence of family-related phenotypes was likely attributed to the combination of the mouse genotype and low-intensity noise. GSH and GSSG are important physiological substrates of ABCC1. The destruction of GSH-GSSG balance in the cochleae of both Abcc1N591S/+ mice and Abcc1N591S/N591S mice during low-intensity noise exposure may result in irreversible damage to the hair cells of the cochleae, consequently leading to hearing loss in mice. The findings offered a potential novel idea for the prevention and management of hereditary hearing loss within this family.

Keywords: Abcc1; autosomal dominant non‐syndromic hearing loss; cochlear ribbon synapse; low‐intensity noise.

MeSH terms

  • Animals
  • Cochlea / metabolism
  • Cochlea / pathology
  • Disease Models, Animal*
  • Female
  • Gene Knock-In Techniques
  • Glutathione / metabolism
  • Hearing Loss / genetics
  • Hearing Loss / pathology
  • Humans
  • Male
  • Mice
  • Multidrug Resistance-Associated Proteins* / genetics
  • Mutation*
  • Noise / adverse effects

Substances

  • Multidrug Resistance-Associated Proteins
  • multidrug resistance-associated protein 1
  • Glutathione