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

Michael D. Weston, Shikha Tarang, Marsha L. Pierce, Umesh Pyakurel, Sonia M. Rocha-Sanchez, JoAnn D McGee, Edward J Walsh, Garrett A. Soukup

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 valuable tool to predict and elucidate miRNA-regulated genes and integrated functional gene expression networks that significantly influence neurosensory cell differentiation, maturation and homeostasis.

Original languageEnglish (US)
Article number3569
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Cochlea
MicroRNAs
Homeostasis
Inner Auditory Hair Cells
Homozygote
Hearing Loss
Outer Auditory Hair Cells
Genes
Germ-Line Mutation
Gene Regulatory Networks
Inner Ear
Microarray Analysis
Cell Differentiation
Down-Regulation
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Weston, M. D., Tarang, S., Pierce, M. L., Pyakurel, U., Rocha-Sanchez, S. M., McGee, J. D., ... Soukup, G. A. (2018). A mouse model of MIR-96, MIR-182 and MIR-183 misexpression implicates MIRNAs in cochlear cell fate and homeostasis. Scientific Reports, 8(1), [3569]. https://doi.org/10.1038/s41598-018-21811-1

A mouse model of MIR-96, MIR-182 and MIR-183 misexpression implicates MIRNAs in cochlear cell fate and homeostasis. / Weston, Michael D.; Tarang, Shikha; Pierce, Marsha L.; Pyakurel, Umesh; Rocha-Sanchez, Sonia M.; McGee, JoAnn D; Walsh, Edward J; Soukup, Garrett A.

In: Scientific Reports, Vol. 8, No. 1, 3569, 01.12.2018.

Research output: Contribution to journalArticle

Weston, MD, Tarang, S, Pierce, ML, Pyakurel, U, Rocha-Sanchez, SM, McGee, JD, Walsh, EJ & Soukup, GA 2018, 'A mouse model of MIR-96, MIR-182 and MIR-183 misexpression implicates MIRNAs in cochlear cell fate and homeostasis', Scientific Reports, vol. 8, no. 1, 3569. https://doi.org/10.1038/s41598-018-21811-1
Weston, Michael D. ; Tarang, Shikha ; Pierce, Marsha L. ; Pyakurel, Umesh ; Rocha-Sanchez, Sonia M. ; McGee, JoAnn D ; Walsh, Edward J ; Soukup, Garrett A. / A mouse model of MIR-96, MIR-182 and MIR-183 misexpression implicates MIRNAs in cochlear cell fate and homeostasis. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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