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Lewis, M.A.* ; Quint, E.* ; Glazier, A.M.* ; Fuchs, H. ; Hrabě de Angelis, M. ; Langford, C.* ; van Dongen, S.* ; Abreu-Goodger, C.* ; Piipari, M.* ; Redshaw, N.* ; Dalmay, T.* ; Moreno-Pelayo, M.A.* ; Enright, A.J.* ; Steel, K.P.*

An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice.

Nat. Genet. 41, 614-618 (2009)
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Progressive hearing loss is common in the human population, but little is known about the molecular basis. We report a new N-ethyl-N-nitrosurea (ENU)-induced mouse mutant, diminuendo, with a single base change in the seed region of Mirn96. Heterozygotes show progressive loss of hearing and hair cell anomalies, whereas homozygotes have no cochlear responses. Most microRNAs are believed to downregulate target genes by binding to specific sites on their mRNAs, so mutation of the seed should lead to target gene upregulation. Microarray analysis revealed 96 transcripts with significantly altered expression in homozygotes; notably, Slc26a5, Ocm, Gfi1, Ptprq and Pitpnm1 were downregulated. Hypergeometric P-value analysis showed that hundreds of genes were upregulated in mutants. Different genes, with target sites complementary to the mutant seed, were downregulated. This is the first microRNA found associated with deafness, and diminuendo represents a model for understanding and potentially moderating progressive hair cell degeneration in hearing loss more generally.
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Publication type Article: Journal article
Document type Scientific Article
Keywords outer hair cell; inner-ear; stereocilia defects; microrna targets; gene-expression; mutant mice; mouse; differentiation; organ; impairment
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 41, Issue: 5, Pages: 614-618 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed