Characterization of the early pathology of cochlear stereocilia in four inbred mouse strains with progressive hearing loss

Histol Histopathol. 2019 Jul;34(7):811-820. doi: 10.14670/HH-18-086. Epub 2019 Jan 24.

Abstract

Objective: Inbred strains of mice offer promising models for understanding the genetic basis of age-related hearing loss (AHL). NOD/LtJ, A/J, DBA/2J and C57BL/6J mice are classical models of age-related hearing loss and exhibit early onset of pathology of AHL. This study was carried out to characterize the early pathology of cochlear stereocilia in the four mouse strains with age-related hearing loss.

Methods: The structural features of stereocilia in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice were observed by scanning electron microscopy (SEM) at age 2, 4, 6 or 8, and 10 or 12 weeks. Meanwhile, auditory-evoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) amplitudes of the mice were measured at various intervals (3, 4, 6, 8, 10 and 12 weeks of age).

Results: The ABR thresholds in NOD/LtJ, A/J and DBA/2J mice increased with age from 3 to 12 weeks. DPOAE amplitudes in NOD/LtJ, A/J, DBA/2J mice were very low at 4 weeks and became negative at 8 weeks at f2 frequency of 17 672 Hz. In addition to the progressive hearing loss, the four mouse strains displayed early onset (at 2 weeks of age) and progressive degeneration of stereocilia in hair cells.

Conclusion: Early degeneration of stereocilia contributes to the functional impairment of hair cells and hearing loss in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice.

MeSH terms

  • Animals
  • Auditory Threshold / physiology
  • Cadherins / genetics
  • Carrier Proteins / genetics
  • Cochlea / pathology
  • Cochlea / ultrastructure*
  • Evoked Potentials, Auditory, Brain Stem
  • Hearing Loss / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred NOD
  • Mice, Inbred Strains
  • Microfilament Proteins / genetics
  • Microscopy, Electron, Scanning
  • Stereocilia / pathology
  • Stereocilia / ultrastructure*
  • Time Factors

Substances

  • Cadherins
  • Carrier Proteins
  • Cdh23 protein, mouse
  • Microfilament Proteins
  • fascin