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Vogl, C.* ; Butola, T.* ; Haag, N.* ; Hausrat, T.J.* ; Leitner, M.G.* ; Moutschen, M.* ; Lefèbvre, P.P.* ; Speckmann, C.* ; Garrett, L. ; Becker, L. ; Fuchs, H. ; Hrabě de Angelis, M. ; Nietzsche, S.* ; Kessels, M.M.* ; Oliver, D.* ; Kneussel, M.* ; Kilimann, M.W.* ; Strenzke, N.*

The BEACH protein LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing.

EMBO Rep. 18, 2015-2029 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Lipopolysaccharide-responsive beige-like anchor protein (LRBA) belongs to the enigmatic class of BEACH domain-containing proteins, which have been attributed various cellular functions, typically involving intracellular protein and membrane transport processes. Here, we show that LRBA deficiency in mice leads to progressive sensorineural hearing loss. In LRBA knockout mice, inner and outer hair cell stereociliary bundles initially develop normally, but then partially degenerate during the second postnatal week. LRBA deficiency is associated with a reduced abundance of radixin and Nherf2, two adaptor proteins, which are important for the mechanical stability of the basal taper region of stereocilia. Our data suggest that due to the loss of structural integrity of the central parts of the hair bundle, the hair cell receptor potential is reduced, resulting in a loss of cochlear sensitivity and functional loss of the fraction of spiral ganglion neurons with low spontaneous firing rates. Clinical data obtained from two human patients with protein-truncating nonsense or frameshift mutations suggest that LRBA deficiency may likewise cause syndromic sensorineural hearing impairment in humans, albeit less severe than in our mouse model.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cochlear Amplification ; Hair Bundle Degeneration ; Progressive Hearing Loss ; Radixin ; Stereociliar Protein Transport; Inner-ear; Synaptic-transmission; Afferent Synapse; Acoustic Trauma; Domain Protein; Stereocilia; Mouse; Gene; Radixin; Neurobeachin
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Quellenangaben Volume: 18, Issue: 11, Pages: 2015-2029 Article Number: , Supplement: ,
Publisher EMBO Press
Publishing Place Hoboken
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)