CYLD deficiency causes auditory neuropathy due to reduced neurite outgrowth

J Clin Lab Anal. 2021 Jun;35(6):e23783. doi: 10.1002/jcla.23783. Epub 2021 May 2.


Background: Auditory neuropathy is a cause of hearing loss that has been studied in a number of animal models. Signal transmission from hair cells to spiral ganglion neurons plays an important role in normal hearing. CYLD is a microtubule-binding protein, and deubiquitinase involved in the regulation of various cellular processes. In this study, we used Cyld knockout (KO) mice and nerve cell lines to examine whether CYLD is associated with auditory neuropathy.

Methods: Hearing of Cyld KO mice was studied using the TDT RZ6 auditory physiology workstation. The expression and localization of CYLD in mouse cochlea and cell lines were examined by RT-PCR, immunoblotting, and immunofluorescence. CYLD expression was knocked down in SH-SY5Y cells by shRNAs and in PC12 and N2A cells by siRNAs. Nerve growth factor and retinoic acid were used to induce neurite outgrowth, and the occurrence and length of neurites were statistically analyzed between knockdown and control groups.

Results: Cyld KO mice had mild hearing impairment. Moreover, CYLD was widely expressed in mouse cochlear tissues and different nerve cell lines. Knocking down CYLD significantly reduced the length and proportion of neurites growing from nerve cells.

Conclusions: The abnormal hearing of Cyld KO mice might be caused by a decrease in the length and number of neurites growing from auditory nerve cells in the cochlea, suggesting that CYLD is a key protein affecting hearing.

Keywords: CYLD; auditory neuropathy; cochlea; hearing; neurite.

MeSH terms

  • Age Factors
  • Animals
  • Cell Line, Tumor
  • Cochlea / physiology
  • Deubiquitinating Enzyme CYLD / genetics*
  • Deubiquitinating Enzyme CYLD / metabolism*
  • Hearing Loss / genetics
  • Hearing Loss, Central / genetics*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Nerve Growth Factor / pharmacology
  • Neurites / drug effects
  • Neurites / physiology
  • Neuronal Outgrowth / physiology*
  • PC12 Cells
  • Rats
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism


  • Nerve Growth Factor
  • CYLD protein, human
  • CYLD protein, mouse
  • CYLD protein, rat
  • Deubiquitinating Enzyme CYLD
  • Ubiquitin Thiolesterase

Supplementary concepts

  • Auditory neuropathy