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Diminuendo -- New mouse model for understanding cause of progressive hearing loss
Date:4/27/2009

The respective microRNA seed region influences the production of sensory hair cells in the inner ear, both in the mouse and in humans. The findings have been published ahead of print in the current online issue of Nature Genetics. This study represents a major step forward in elucidating the common phenomenon of progressive hearing loss, opening up new avenues for treatment.

Scientists of Helmholtz Zentrum Mnchen, led by Professor Martin Hrab de Angelis, director of the Institute of Experimental Genetics, 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 Dr. Helmut Fuchs, who conceived the idea of this mouse model and who is scientific -technical head of the German Mouse Clinic at Helmholtz Zentrum Mnchen.

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, Martin Hrab de Angelis and his colleagues in the German Mouse Clinic can thus identify mutants that develop diseases similar to human diseases. They made the diminuendo mouse model available to colleagues of the Wellcome Trust Sanger Institute in Cambridge, UK, who based on specific characterizations ultimately found the association with the miR-96 mutation.

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Contact: Sven Winkler
sven.winkler@helmholtz-muenchen.de
0049-893-187-3946
Helmholtz Zentrum Mnchen - German Research Center for Environmental Health
Source:Eurekalert

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