A mouse model of miR-96, miR-182 and miR-183 misexpression implicates miRNAs in cochlear cell fate and homeostasis

Scientific Reports
Michael D WestonGarrett A Soukup

Abstract

Germline mutations in Mir96, one of three co-expressed polycistronic miRNA genes (Mir96, Mir182, Mir183), cause hereditary hearing loss in humans and mice. Transgenic FVB/NCrl- Tg(GFAP-Mir183,Mir96,Mir182)MDW1 mice (Tg1MDW), which overexpress this neurosensory-specific miRNA cluster in the inner ear, were developed as a model system to identify, in the aggregate, target genes and biologic processes regulated by the miR-183 cluster. Histological assessments demonstrate Tg1MDW/1MDW homozygotes have a modest increase in cochlear inner hair cells (IHCs). Affymetrix mRNA microarray data analysis revealed that downregulated genes in P5 Tg1MDW/1MDW cochlea are statistically enriched for evolutionarily conserved predicted miR-96, miR-182 or miR-183 target sites. ABR and DPOAE tests from 18 days to 3 months of age revealed that Tg1MDW/1MDW homozygotes develop progressive neurosensory hearing loss that correlates with histologic assessments showing massive losses of both IHCs and outer hair cells (OHCs). This mammalian miRNA misexpression model demonstrates a potency and specificity of cochlear homeostasis for one of the dozens of endogenously co-expressed, evolutionally conserved, small non-protein coding miRNA families. It should be a ...Continue Reading

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Citations

Jul 31, 2019·Molecular Neurobiology·Samantha A BanksGarrett A Soukup
Dec 16, 2020·Disease Models & Mechanisms·Morag A LewisKaren P Steel

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Datasets Mentioned

BETA
GSE95579

Methods Mentioned

BETA
transgenic
fluorescence imaging
PCR
transfections
genotyping
Confocal microscopy
biopsies
scanning electron microscopy
Assay
chips

Software Mentioned

MicroArray US Gui interface
Limma Package
SPSS
Affymetix
Sylamer
TargetScan
Affymetrix MoGene
MicroArraysRUS Gui
Linear Model for Microarray Data ( Limma ) Package
R

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