A Systematic Review of Genes Affecting Endocochlear Potential.

PURPOSE: Hearing loss is highly heterogeneous. Any one of hundreds of genes and dozens of cell types can be involved in the pathological processes in the auditory system. One class of hearing loss results from a reduction of the endocochlear potential (EP), a voltage maintained in the endolymph that bathes the upper surface of the sensory hair cells in the cochlea. Understanding the landscape of genes involved in reduced EP will be useful in developing targeted therapies for this type of hearing loss. Here we review these genes.

METHODS

Research articles that report genes impacting EP in mutant mice were collated using several different approaches. Cell type-specific expression and patterns in their biological function were investigated.

RESULTS

We report 55 genes associated with reduced EP as well as 43 genes shown to underlie deafness but with no change in EP. We show that of these 55 reduced EP genes, 27 are linked to deafness in humans and therefore these patient populations are candidates for having a reduced EP. We demonstrate that the expression of reduced EP genes is not clustered to a particular cell type within the stria vascularis or organ of Corti.

CONCLUSION

This analysis highlights the broad range of expression patterns and functions of genes involved in generating and maintaining the mammalian EP. Furthermore, the lists presented here can inform the direction of translational research for different forms of human hearing loss.