Connexin32 can restore hearing in connexin26 deficient mice

• Published in: European journal of cell biology Vol. 90; no. 10; pp. 817 - 824
• Main Authors: Degen, Joachim, Schütz, Melanie, Dicke, Nikolai, Strenzke, Nicola, Jokwitz, Melanie, Moser, Tobias, Willecke, Klaus
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.10.2011
• Subjects: Animals; beta-Galactosidase - biosynthesis; beta-Galactosidase - genetics; Cochlea; Connexin 26; Connexin 30; Connexins - deficiency; Connexins - genetics; Connexins - metabolism; Cx26; Cx32; Deafness; Deafness - genetics; Evoked Potentials, Auditory, Brain Stem; Gap Junction beta-1 Protein; Gap junctions; Gene Dosage; Gene Expression; Genes, Reporter; Genetic Engineering; Inner ear; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Knockout; Mice, Transgenic; Otogelin-Cre; Protein Isoforms - genetics; Protein Isoforms - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Spiral Ligament of Cochlea - metabolism; Stria Vascularis - cytology; Stria Vascularis - metabolism; Deafness; Cx32; Gap junctions; Cochlea; Cx26; Otogelin-Cre; Inner ear
• ISSN: 0171-9335; 1618-1298
• DOI: 10.1016/j.ejcb.2011.05.001

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.