A mouse model of miR-96, miR-182 and miR-183 misexpression implicates miRNAs in cochlear cell fate and homeostasis
| Autor: | Umesh Pyakurel, Garrett A. Soukup, JoAnn McGee, Marsha L. Pierce, Shikha Tarang, Michael D. Weston, Edward J. Walsh, Sonia M. Rocha-Sanchez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Science Cellular differentiation Hearing Loss Sensorineural Mice Transgenic Cell fate determination Biology Article 03 medical and health sciences Mice Germline mutation microRNA medicine otorhinolaryngologic diseases Animals Homeostasis Humans Inner ear RNA Messenger Cochlea Regulation of gene expression Multidisciplinary Hair Cells Auditory Inner Microarray analysis techniques Cell Differentiation Microarray Analysis Cell biology Disease Models Animal MicroRNAs 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Ear Inner Medicine sense organs |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-19 (2018) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|