Remodeling of the Inner Hair Cell Microtubule Meshwork in a Mouse Model of Auditory Neuropathy AUNA1

eNeuro. 2016 Dec 29;3(6):ENEURO.0295-16.2016. doi: 10.1523/ENEURO.0295-16.2016. eCollection 2016 Nov-Dec.


Auditory neuropathy 1 (AUNA1) is a form of human deafness resulting from a point mutation in the 5' untranslated region of the Diaphanous homolog 3 (DIAPH3) gene. Notably, the DIAPH3 mutation leads to the overexpression of the DIAPH3 protein, a formin family member involved in cytoskeleton dynamics. Through study of diap3-overexpressing transgenic (Tg) mice, we examine in further detail the anatomical, functional, and molecular mechanisms underlying AUNA1. We identify diap3 as a component of the hair cells apical pole in wild-type mice. In the diap3-overexpressing Tg mice, which show a progressive threshold shift associated with a defect in inner hair cells (IHCs), the neurotransmitter release and potassium conductances are not affected. Strikingly, the overexpression of diap3 results in a selective and early-onset alteration of the IHC cuticular plate. Molecular dissection of the apical components revealed that the microtubule meshwork first undergoes aberrant targeting into the cuticular plate of Tg IHCs, followed by collapse of the stereociliary bundle, with eventual loss of the IHC capacity to transmit incoming auditory stimuli.

Keywords: cochlea; cuticular plate; deafness; diap3; diaphanous.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • HEK293 Cells
  • Hair Cells, Auditory, Inner / metabolism*
  • Hair Cells, Auditory, Inner / pathology
  • Hearing Loss, Central / metabolism*
  • Hearing Loss, Central / pathology
  • Humans
  • Membrane Potentials / physiology
  • Mice, Transgenic
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism*
  • Microtubules / pathology
  • NADPH Dehydrogenase / genetics
  • NADPH Dehydrogenase / metabolism
  • Otoacoustic Emissions, Spontaneous / physiology
  • Potassium / metabolism
  • Synaptic Vesicles / metabolism
  • Synaptic Vesicles / pathology


  • Microtubule-Associated Proteins
  • Dia2 protein, mouse
  • NADPH Dehydrogenase
  • Potassium
  • Calcium

Supplementary concepts

  • Auditory neuropathy