An international group of researchers have identified the gene that acts as a key regulator for special cells needed in hearing. The discovery of this gene (Ikzf2) will help researchers better understand this unique type of cell that is needed for hearing and potentially develop treatments for common age-related hearing loss.
"Outer hair cells are the first inner ear cells lost as we age. Age-related hearing loss happens to everyone. Even a 30-year-old has lost some of the outer hair cells that sense higher pitch sounds. Simply exposure to sound, especially loud ones, eventually causes damage to these cells," said the senior author whose research will be published in the journal Nature.
The inner ear has two kinds of sensory hair cells required for hearing. The inner hair cells convert sounds to neural signals that travel to the brain. This compares to outer hair cells, which function by amplifying and tuning sounds. Without outer hair cells, sound is severely muted and inner hair cells don't signal the brain. Loss of outer hair cells is the major cause of age-related loss of hearing.
The group took a bioinformatics and functional genomics approach to discover a gene critical for the regulation of genes involved in outer hair cell development. They studied mice from the Harwell Aging Screen to identify mice with hearing loss. Bowl identified mice with an early-onset hearing loss caused by an outer hair cell deficit. When the two groups realized that they were studying the same gene, they began to collaborate to discover its biological function and role in outer hair cell development. The gene is Ikzf2 gene, which encodes helios. Helios is a transcription factor, a protein that controls the expression of other genes. The mutation in the mice changes one amino acid in a critical part of the protein, which impaired the transcriptional regulatory activity of helios in the mice.
To test if helios could drive the differentiation of outer hair cells, the researchers introduced a virus engineered to overexpress helios into the inner ear hair cells of newborn mice. As a result, some of the mature inner hair cells became more like outer hair cells. In particular, the inner hair cells with an excess of helios started making the protein prestin and exhibited electromotility, a property limited to outer hair cells. Thus, helios can drive inner hair cells to adopt critical outer hair cell characteristics..
http://www.medschool.umaryland.edu/news/2018/UMSOM-Expert-Discovers-Key-Gene-in-Cells-Associated-with-Age-Related-Hearing-Loss.html
https://www.nature.com/articles/s41586-018-0728-4
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