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Gene expression profiles in the inner ears of Fscn2 knockout mice compared with the control mice

ABSTRACT: Fscn2-/- mouse is a typical model of age-related hearing loss which exhibits progressive hearing impairment and outer hair cell loss from 3 weeks of age. To investigate the molecular mechanism of hearing loss in Fscn2 knockout mice, gene expression profiling was performed on the inner ears for Fscn2+/+ and Fscn2-/- mice at 8 weeks of age using microarray analysis. Hearing screening tests at 8 weeks of age showed that the auditory brainstem response thresholds of Fscn2-/- mice were increased to 70-75 dB SPL at stimuli of click, while those of Fscn2+/+ mice were within the normal range(< 55 dB SPL). Microarray analysis identified a total of 244 differentially expressed mRNAs, including 72 upregulated and 172 downregulated genes, and a total of 688 differentially expressed lncRNAs, including 300 upregulated and 388 downregulated genes in Fscn2-/- mice, compared to Fscn2+/+ mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE252226 | GEO | 2024/01/02

REPOSITORIES: GEO

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Project description:We performed a microarray analysis of auditory midbrain (inferior colliculus, IC) mRNA from young adult CBA mice (controls) with good hearing, middle aged (MA) with good hearing, and old mild (MP) and severe (SP) presbycusic CBA mice. Fold Change data derived from RMA normalization revealed that the overall GABA receptor alpha 6 expression profiles for MA, MP and SP were down-regulated relative to young adult controls with good hearing. Relative real-time PCR for five GABA receptors confirmed this age-related down regulation quantitatively. Functional hearing data: Auditory Brainstem Responses (ABR) enriched the analysis to select the probe-sets that changed with age and hearing loss by the linear regression best-fit line model technique. GABA receptor genotype-phenotype correlations with auditory functional data indicated that GABA-receptor subtypes are under expressed in SP mice. Hierarchical clustering (HC) analyses yielded statistical significance of normalized GeneChip data Real-time PCR showed that Gabra6, GABA B receptor 1 (Gabbr1), and Gaba transporter protein Slc32a1 may be involved in physiological changes that occur in age-related hearing loss. Presbycusis – age-related hearing loss – is the number one communicative disorder of our aged population. In this study we analyzed gene expression for a set of GABA receptors in the inferior colliculus of aging CBA mice using the Affymetrix GeneChip MOE430A. Functional phenotypic hearing changes from RMA normalized microarray data (39 replicates) in four age-groups, Young Controls and Middle aged mice with good hearing, mild and sever e presbycusis from old mice. Fold change gene expression derived from RMA normalized data were first subjected to one-way ANOVA, and then linear regression was performed. The selected gene expression changes were confirmed by relative real-time relative to young adult controls with good hearing. Statistically significant and real time PCR confirmed GABA receptor genes; Gabra6, GABA B receptor 1 (Gabbr1), and Gaba transporter protein Slc32a1, may be involved in physiological changes that occur in age-related hearing loss. Lastly, gene expression measures of each age group were correlated with pathway/network relationships relevant to the inferior colliculus using Pathway Architect, to identify key pathways consistent with the gene expression changes observed In the study of Expression changes in IC GABA receptors in the Auditory Midbrain of young adult and aging presbycusis mice total of thirty nine chips were used. The normal aging mice were in Four groups Young adults Controls with good hearing (8 mice, 8 MOE430A GeneChips), Middle aged group with good hearing ( 17 mice, 17 MOE430A GeneChips), Mild Presbycusis with limited hearing loss (9 mice, 9 MOE430A GeneChips) and Severe Presbycusis (5 mice, 5 MOE430A GeneChips).

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Gene expression profiles in the inner ears of Fscn2 knockout mice compared with the control mice

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