Project description:Age-related hearing loss is a progressive sensorineural hearing loss that occurs as people get older. Degeneration of the organ of Corti and atrophy of the lateral wall of the scala media in the inner ear are the two primary causes. Transcriptome analysis has emerged as a powerful tool in revealing the genetic and molecular profile of a cell or a population of cells during aging in organism models, animals and humans. Comparison of transcriptomes between young and older animals have identified many common genes and pathways that are associated with aging and longevity. We used RNA-seq to examine changes in gene expression profiles of the stria vascularis between 9- and 26-month-old CBA mice. Our transcriptome analysis provides a rich resource for mechanistic studies of biological aging of stria vascularis.
Project description:To see for differential expression of genes in the stria vascularis of wild type and pendrin knockout mice Experiment Overall Design: Six samples in total of stria vascularis RNA were analyzed. Triplicates from wild type and pendrin knockout mice were run and analyzed.
Project description:Determination of differential expression of genes in the stria vascularis of pendrin (Slc26a4) heterozygous and knockout mice before the onset of hearing at postnatal day 10 (P10). Experiment Overall Design: A total of Six samples of stria vascularis RNA obtained from P10 mice were analyzed. Triplicates from pendrin (Slc26a4) heterozygous and knockout mice were run and analyzed.
Project description:Alternative splicing contributes to gene expression dynamics in many tissues, yet its role in auditory development remains unclear. We performed whole exome sequencing in individuals with sensorineural hearing loss (SNHL) and identified pathogenic mutations in Epithelial Splicing Regulatory Protein 1 (ESRP1). Patient derived induced pluripotent stem cells showed alternative splicing defects consistent with impaired ESRP1 function. To determine how mutations in ESRP1 cause hearing loss we evaluated Esrp1-/- mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation and cell fate specification. Transcriptome analysis revealed impaired expression and splicing of genes with essential roles in inner ear development and auditory function. In particular, aberrant splicing of Fgfr2 blocked stria vascularis formation due to erroneous ligand usage, which was corrected by reducing Fgf9 gene dosage. These findings implicate mutations in ESRP1 as a novel cause of SNHL and demonstrate the complex interplay between alternative splicing, inner ear development, and auditory function.
Project description:To clarify the effect of Mitf mutation on stria vascularis transcriptome and identify downstream-genes of Mitf pathway which responsible for hearing development, we employed high-throughput sequencing to analyze the transcriptome of MitfR/r and Mitfr/r stria vascularis.
Project description:To clarify the effect of Mitf mutation on stria vascularis transcriptome and identify downstream-genes of Mitf pathway which responsible for hearing development, we employed high-throughput sequencing to analyze the transcriptome of MitfR/r and Mitfr/r stria vascularis. Compare the transcriptome difference between MITF mutated homozygous and heterozygous pigs.
