English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

ABSTRACT  The microRNA miR-96 is important for hearing, as point mutations in humans and mice result in dominant progressive hearing loss.  Mir96  is expressed in sensory cells along with  Mir182  and  Mir183 , but the roles of these closely-linked microRNAs are as yet unknown. Here, we analyse mice carrying null alleles of  Mir182 , and of  Mir183  and  Mir96  together to investigate their roles in hearing. We found that  Mir183 / 96  heterozygous mice had normal hearing and homozygotes were completely deaf with abnormal hair cell stereocilia bundles and reduced numbers of inner hair cell synapses at 4 weeks of age.  Mir182  knockout mice developed normal hearing then exhibited progressive hearing loss. Our transcriptional analyses revealed significant changes in a range of other genes, but surprisingly there were fewer genes with altered expression in the organ of Corti of  Mir183/96  null mice compared with our previous findings in  Mir96 Dmdo   mutants, which have a point mutation in the miR-96 seed region. This suggests that the more-severe phenotype of  Mir96 Dmdo   mutants compared with  Mir183 / 96  mutants, including progressive hearing loss in  Mir96 Dmdo   heterozygotes, is likely to be mediated by the gain of novel target genes in addition to the loss of its normal targets. We propose three mechanisms of action of mutant miRNAs: loss of targets that are normally completely repressed, loss of targets for which transcription is normally buffered by the miRNA, and gain of novel targets. Any of these mechanisms could lead to a partial loss of a robust cellular identity and consequent dysfunction.

Hearing impairment due to Mir183/96/182 mutations suggests both loss-of-function and gain-of-function effects