4.6 Article

Connexin30-Deficiency Causes Mild Hearing Loss With the Reduction of Endocochlear Potential and ATP Release

Journal

FRONTIERS IN CELLULAR NEUROSCIENCE
Volume 15, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2021.819194

Keywords

connexin30; hearing loss; connexin26; stria vascularis; endocochlear potential

Categories

Funding

  1. National Natural Science Foundation of China-China Academy of General Technology Joint Fund for Basic Research [81873698, 82000977]
  2. Shanghai Sailing Program [20YF1428900]

Ask authors/readers for more resources

This study established a new Cx30 knockout mouse model using CRISPR/Cas9 technology, and found that the lack of Cx30 can cause mild hearing loss with approximately 30% reduction of Cx26. This suggests that Cx30 may play an important role in hearing development.
GJB2 and GJB6 are adjacent genes encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, with overlapping expressions in the inner ear. Both genes are associated with the commonest monogenic hearing disorder, recessive isolated deafness DFNB1. Cx26 plays an important role in auditory development, while the role of Cx30 in hearing remains controversial. Previous studies found that Cx30 knockout mice had severe hearing loss along with a 90% reduction in Cx26, while another Cx30 knockout mouse model showed normal hearing with nearly half of Cx26 preserved. In this study, we used CRISPR/Cas9 technology to establish a new Cx30 knockout mouse model (Cx30(-/-)), which preserves approximately 70% of Cx26. We found that the 1, 3, and 6-month-old Cx30(-/-) mice showed mild hearing loss at full frequency. Immunofluorescence and HE staining suggested no significant differences in microstructure of the cochlea between Cx30(-/-) mice and wild-type mice. However, transmission electron microscopy showed slight cavity-like damage in the stria vascularis of Cx30(-/-) mice. And Cx30 deficiency reduced the production of endocochlear potential (EP) and the release of ATP, which may have induced hearing loss. Taken together, this study showed that lack of Cx30 can lead to hearing loss with an approximately 30% reduction of Cx26 in the present Cx30 knockout model. Hence, Cx30 may play an important rather than redundant role in hearing development.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available