An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice
| Autor: | Martin Hrabé de Angelis, Morag A. Lewis, Anton J. Enright, Karen P. Steel, Stijn van Dongen, Cordelia Langford, Tamas Dalmay, Anne M Glazier, Nick Redshaw, Cei Abreu-Goodger, M A Moreno-Pelayo, Elizabeth Quint, Helmut Fuchs, Matias Piipari |
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| Přispěvatelé: | Enright, Anton [0000-0002-6090-3100], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Heterozygote
Hearing loss Population Mutant DNA Mutational Analysis Molecular Sequence Data Mice Inbred Strains Biology medicine.disease_cause Transfection Article 03 medical and health sciences Mice 0302 clinical medicine Hair Cells Auditory Genetics medicine otorhinolaryngologic diseases Gene silencing Animals education Hearing Loss 030304 developmental biology 0303 health sciences education.field_of_study Mutation Base Sequence Microarray analysis techniques Heterozygote advantage Molecular biology Mice Inbred C57BL MicroRNAs medicine.anatomical_structure Ethylnitrosourea Hair cell medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Nature genetics |
| ISSN: | 1546-1718 1061-4036 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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