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A Collaborative Search for New Genes for Non-Syndromic Deafness

ABSTRACT: A Collaborative Search for New Genes for Non-Syndromic Deafness

PROVIDER: PRJNA1131023 | ENA |

REPOSITORIES: ENA

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Single cell RNA-seq of cochlear tissues from Tmie+/- and Tmie-/- mice, a model for recessive non-syndromic deafness model 6.

Project description:Deafness is the most common form of sensory impairment in humans and frequently caused by defects in hair cells of the inner ear. Here we demonstrate that in a mouse model for recessive non-syndromic deafness (DFNB6), inactivation of Tmie in hair cells disrupts gene expression in the neurons that innervate them. This includes genes regulating axonal pathfinding and synaptogenesis, two processes that are disrupted in the inner ear of the mutant mice. Similar defects are observed in mouse models for deafness caused by mutations in other genes with primary functions in hair cells. Gene therapy targeting hair cells restores hearing and inner ear circuitry in DFNB6 model mice. We conclude that hair cell function is crucial for the establishment of peripheral auditory circuitry. Treatment modalities for deafness thus need to consider restoration of the function of both hair cells and neurons, even when the primary defect occurs in hair cells.

2024-11-10 | GSE281207 | GEO

The pathogenesis of common Gjb2 mutation associated with human hereditary deafness in mice

Project description:Mutations in GJB2 (Gap junction protein beta 2) are the most common genetic cause of non-syndromic hereditary deafness in humans, especially the 35delG and 235delC mutations. Owing to the homozygous-lethal of Gjb2 mutation in mice, there are currently no perfect mouse models carrying Gjb2 mutation to mimic human hereditary deafness and unveil the pathogenesis. Here, we first constructed heterozygous mutant mice, Gjb2+/35delG and Gjb2+/235delC, through androgenic haploid embryonic stem cells (AG-haESCs) mediated semi-cloning technology, which showed normal hearing function at P28. Furthermore, a homozygous mutant mouse model, Gjb235delG/35delG, was generated via enhanced tetraploid embryo complementation, which exhibited profound hearing loss like human patients at P14. Mechanism analysis showed that Gjb2 35delG disrupts the formation of intercellular gap junction channel and tunnel of Corti, and hair cell mechanotransduction, rather than the development of hair cells. Collectively, our study provides ideal mouse models for understanding the pathogenic mechanism and opens up a new avenue for investigating the treatment for DFNB1A-related hereditary deafness.

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MicroRNA and mRNA integrated transcriptional analysis in a Cx30-/- mouse model of non-syndromic hearing loss and deafness [miRNA]

Project description:The GJB6 gene is located just 35 kb telomeric to GJB2 in the so-called nonsyndromic hearing loss and deafness locus 1 (DFNB1). Knock out mouse models confirmed that inner ear expression of their protein products, connexin 30 (Cx30) and connexin 26 (Cx26), is crucial for hearing acquisition and normal development of the organ of Corti, however the coordinated regulation mechanism of Cx26 and Cx30 expression in the cochlea remains unclear. To investigate the mechanism underlying the etiopathogenesis of DFNB1, we used a microRNA (miRNA) and mRNA integrated expression profiling analysis on Cx30 -/- mice, which represent a model for humans in which large deletions in the DFNB1 locus lead to the down-regulation of both connexins and profound deafness.

2020-12-29 | GSE151368 | GEO

MicroRNA and mRNA integrated transcriptional analysis in a Cx30-/- mouse model of non-syndromic hearing loss and deafness [mRNA]

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Deep intronic homozygous variation in PSMC3, a subunit of the 19S proteasome regulatory complex, causes a syndromic neurosensory disorder combining deafness and cataract

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MicroRNA and mRNA integrated transcriptional analysis in a Cx30-/- mouse model of non-syndromic hearing loss and deafness

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Project description:The main goal of the research was to find some new biomarkers for the monitoring of the Minimal Residual Disease in Acute Lymphoblastic Leukemia patients. Keywords: Search for new Biomarkers

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