Hearing Loss Caused By Genes

Photo: An ear

The mouse model "diminuendo"
might help to find treatments for
hearing loss; © SXC

Scientists, led by Professor Martin Hrabé de Angelis, have developed a new mouse model with a genetic mutant in which a single base of a specific microRNA seed region has been altered. Mice carrying this miR-96 mutation suffer progressive hearing loss as they get older. Moreover, if they carry two of these mutants, their sensory hair cells are impaired from birth on.

A number of genes associated with hearing loss were already known. "However, we were very surprised when with our new mouse model we discovered this new class of genes – microRNA – as genetic cause for this clinical picture," explained Helmut Fuchs, who conceived the idea of this mouse model.

The new mouse model is called diminuendo, named after the term in music theory meaning "becoming gradually softer". The mice were bred using the ENU method in which the male mice are administered N-ethyl-N-nitrosurea (ENU), thus influencing the DNA of their sperm. Successor generations develop dominant or recessive mutations. Using methods like these, Hrabé de Angelis and his colleagues can thus identify mutants that develop diseases similar to human diseases. They made the diminuendo mouse model available to other researchers, who – based on specific characterisations – ultimately found the association with the miR-96 mutation.

"We assume that our mouse model will be of far-reaching significance for the development of treatment strategies against genetically caused progressive hearing loss in humans," Fuchs explained. Colleagues from Spain hope the same. They have already performed first examinations on patients diagnosed with progressive hearing loss. In them, the microRNA cluster Mirn96 was mutated in the same seed region as in the mouse model. Now, with the aid of this mouse model, the international research consortium hopes to identify factors which are necessary for long-term survival of hair cells and thus to find new approaches for treatment of progressive hearing loss.

MEDICA.de; Source: Helmholtz Zentrum München - German Research Center for Environmental Health