Connexin32 can restore hearing in connexin26 deficient mice
| Autor: | Klaus Willecke, Joachim Degen, Nikolai Dicke, Melanie Jokwitz, Nicola Strenzke, Tobias Moser, Melanie Schütz |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Gene isoform
Histology Mutant Gene Dosage Connexin Gene Expression Mice Transgenic Biology Deafness Connexins Pathology and Forensic Medicine 03 medical and health sciences Mice 0302 clinical medicine Transcription (biology) Genes Reporter otorhinolaryngologic diseases Recombinase medicine Connexin 30 Evoked Potentials Auditory Brain Stem Animals Protein Isoforms Inner ear Gene Cochlea 030304 developmental biology Genetics Mice Knockout 0303 health sciences Membrane Glycoproteins Stria Vascularis Cell Biology General Medicine beta-Galactosidase Recombinant Proteins Cell biology Connexin 26 medicine.anatomical_structure Spiral Ligament of Cochlea sense organs Genetic Engineering 030217 neurology & neurosurgery |
| Zdroj: | European journal of cell biology. 90(10) |
| ISSN: | 1618-1298 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect