Connexin32 Can Restore Hearing in connexin26 Deficient Mice

Eur J Cell Biol. 2011 Oct;90(10):817-24. doi: 10.1016/j.ejcb.2011.05.001. Epub 2011 Aug 2.


Functional gap junction channels composed of certain connexin proteins are essential for the function of the cochlea. Homozygous deficiency in the Gjb2 (mice) or GJB2 (human) gene coding for connexin26 (Cx26) in the cochlea leads to hearing impairment in mice and humans, respectively. Here we have studied the functional equivalence of Cx26 and connexin32 (Cx32) isoforms in the cochlea. We analyzed a conditional mouse mutant in which the Gjb2 coding DNA was exchanged by LacZ DNA coding for the reporter protein beta-galactosidase. This allowed us to follow the unrestricted and cell type specific expression of Gjb2 promoter activity. After inner ear specific, Otogelin-Cre recombinase mediated deletion of the loxP-site-flanked LacZ coding DNA, transcription of the Gjb1 gene, coding for Cx32 was activated by the Gjb2 promoter. Interbreeding of these mice with conditional Gjb2 null mice resulted in animals in which Cx32 instead of Cx26 protein is expressed in the non-sensory epithelial network of the cochlea. When we analyzed the auditory function in these mice, we found that the expression of Cx32 protein is sufficient to support hearing in the absence of Cx26. Thus Cx32 can functionally replace Cx26 in the mouse cochlea resulting in almost normal hearing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Connexin 26
  • Connexin 30
  • Connexins / deficiency*
  • Connexins / genetics*
  • Connexins / metabolism
  • Deafness / genetics*
  • Evoked Potentials, Auditory, Brain Stem
  • Gene Dosage
  • Gene Expression
  • Genes, Reporter
  • Genetic Engineering
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Recombinant Proteins / genetics*
  • Recombinant Proteins / metabolism
  • Spiral Ligament of Cochlea / metabolism
  • Stria Vascularis / cytology
  • Stria Vascularis / metabolism
  • beta-Galactosidase / biosynthesis
  • beta-Galactosidase / genetics


  • Connexin 30
  • Connexins
  • DFNA3 protein, human
  • Gjb2 protein, mouse
  • Gjb6 protein, mouse
  • Membrane Glycoproteins
  • Otog protein, mouse
  • Protein Isoforms
  • Recombinant Proteins
  • connexin 32
  • Connexin 26
  • beta-Galactosidase