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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)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter outer hair cell; inner-ear; stereocilia defects; microrna targets; gene-expression; mutant mice; mouse; differentiation; organ; impairment
Sprache englisch
Veröffentlichungsjahr 2009
HGF-Berichtsjahr 2009
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Zeitschrift Nature Genetics
Quellenangaben Band: 41, Heft: 5, Seiten: 614-618 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500600-003
DOI 10.1038/ng.369
Scopus ID 67349132265
PubMed ID 19363478
Erfassungsdatum 2009-07-09
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