A new study has discovered how a mutation in a receptor for thyroid hormone can cause accelerated hearing loss in juvenile mice. Published in Science Signalling, the work demonstrates the important role of thyroid hormone TRα1 in proper hearing. Researchers at the Institute for Neurosciences of Montpellier in France, who conducted the study, call for further research into the impact of similar mutations on human hearing.
Thyroid hormone linked to deafness
Thyroid hormone plays an important role in the body’s metabolic processes. It affects every cell and all the organs in the body and is involved in heart rate, body temperature and brain development. The two main hormones the thyroid releases — thyroxine (T4) and triiodothyronine (T3) — collectively make up thyroid hormone.
In addition, thyroid hormone supports the proper development of the cochlea and auditory system.
Previous research has linked deafness in humans to mutations in TRb1 and TRb2, which are thyroid hormone receptors in the nuclei of cells.
The new study establishes that mutations in another thyroid hormone receptor, called TRa1, can also affect hearing in juvenile mice.
Abnormal cochlear outer hair cells
To test whether TRα1 also affects hearing function, the researchers used mice heterozygous for a frameshift mutation in Thra that is similar to human THRA mutations and reduces tissue sensitivity to thyroid hormone.
The mice studied carried a dominant-negative allele of the gene that encodes TRa1, similar to several mutations identified in its human counterpart THRA.
These mice showed high-frequency hearing loss even as juveniles, and their hearing loss accelerated more quickly with age compared with their wild-type littermates.
Microscopic analysis of the inner ears of the mutant mice revealed that the outer hair cells, which reside in the cochlea, showed abnormal aspects. A regular structure of the hair bundles enables these cells to amplify sound signals. However, the cochlear outer hair cells in the mutant mice were absent or misoriented. Ultrastructural examination revealed increased numbers of mitochondria with fragmented morphology and autophagic vacuoles in these hair cells and auditory nerve fibres.
Further studies showed that the potassium channel Kcnq4, an outer hair cell survival factor, was abnormally distributed in the cells. The cells displayed high levels of oxidative stress and were susceptible to death.
TRα1 and age-related hearing loss
The study demonstrated that a disease-associated form of TRα1 interferes with the proper development and function of cochlear outer hair cells. This suggests that patients with TRHA mutations may be at increased risk for age-related hearing loss.
“These findings suggest that patients with THRA mutations may present underdiagnosed, mild hearing loss and may be more susceptible to age-related hearing loss,” the authors write.
Written by Poppy Jayne Morgan, Front Line Genomics
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