Dataset Information

Otitis media impacts hundreds of mouse middle and inner ear genes.

ABSTRACT:

Objective

Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.

Methods

To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes.

Results

Statistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear.

Conclusion

Whole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media.

SUBMITTER: MacArthur CJ

PROVIDER: S-EPMC3790799 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Otitis media impacts hundreds of mouse middle and inner ear genes.

MacArthur Carol J CJ Hausman Fran F Kempton J Beth JB Choi Dongseok D Trune Dennis R DR

PloS one 20131004 10

<h4>Objective</h4>Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.<h4>Methods</h4>To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-kil ...[more]

PMID: 24124478

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Project description:Objective: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition. Methods: To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes. Results: Statistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear. Conclusion: Whole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media. There are 8 control samples and 9 samples trans-tympanically injected with H flu 10e9 for 6 hours. Each sample is from a single animal.

Project description:Objective: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition. Methods: To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes. Results: Statistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear. Conclusion: Whole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media. There are 6 control samples and 8 samples trans-tympanically injected with H flu 10e9 for 6 hours. Each sample is a pool of 4 animals

Project description:High incidence of chronic otitis media is associated with human craniofacial syndromes, suggesting that defects in the formation of the middle ear and associated structures can have a knock-on effect on the susceptibility to middle ear inflammation. Patients with branchio-oto-renal (BOR) syndrome have several defects in the ear leading to both sensorineural and conductive hearing loss, including otitis media. 40% of BOR syndrome cases are due to Eya1 haploinsufficiency, with mouse models affecting Eya1, mimicking many of the defects found in patients. Here, we characterize the onset, consequences, and underlying causes of chronic otitis media in Eya1 heterozygous mice. Cavitation defects were evident in these mice from postnatal day (P)11 onwards, with mesenchyme around the promontory and attic regions of the middle ear space. This mesenchyme was still prominent in adult Eya1 heterozygous mice, while the wild-type littermates had fully aerated ears from P14 onwards. MicroCT analysis highlighted a significantly smaller bulla, confirming the link between bulla size defects and the ability of the mesenchyme to retract successfully. Otitis media was observed from P14, often presenting unilaterally, resulting in hyperplasia of the middle ear mucosa, expansion of secretory cells, defects in the motile cilia, and changes in basal epithelial cell markers. A high incidence of otitis media was identified in older mice but only associated with ears with retained mesenchyme. To understand the impact of the environment, the mouse line was rederived onto a super-clean environment. Cavitation defects were still evident at early stages, but these generally resolved over time, and importantly, no signs of otitis media were observed at 6 weeks. In conclusion, we show that a small bulla size is closely linked to defects in cavitation and the presence of retained mesenchyme. A delay in retraction of the mesenchyme predates the onset of otitis media, making the ears susceptible to its development. Early exposure to OM appears to exacerbate the cavitation defect, with mesenchyme evident in the middle ear throughout the animal's life. This highlights that permanent damage to the middle ear can arise as a consequence of the early onset of OM.

Project description:BackgroundProteins found in middle ear effusion play crucial roles in the physiological and pathological processes of otitis media with effusion (OME), influencing the etiology and clinical characteristics of this disease. The qualitative and quantitative composition of these proteins depending on the underlying pathogenesis of middle ear effusion. Understanding their physiological and pathological functions is of great importance.MethodsWe collected samples from 19 volunteers diagnosed with OME. After offline separation using high-pH reversed-phase liquid chromatography (RPLC), the pooled sample was subjected to LC-MS/MS analysis to obtain a comprehensive profile of the OME proteome. Functional analysis was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA) annotations. Data-independent acquisition (DIA) technology was utilized to analyze samples and fix whether the OME proteome could replicate the pathophysiological features associated with this disease. We conducted a differential proteomic analysis between patients with simple OME and patients who had received radiotherapy. The radiotherapy-reduced group was further divided into two subgroups: nasopharyngeal carcinoma (NPC) and other types of carcinoma. Parallel reaction monitoring (PRM) technology was used for validation of 36 differentially expressed proteins (DEPs).ResultsA number of 732 proteins were identified in the OME proteome database. Among them, 527 proteins were quantified using peak intensity-based semi-quantification (iBAQ), covering a wide dynamic range of approximately 8 orders of magnitude. Based on the functional analysis, we proposed a hypothetical mechanism of OME.ConclusionThis study managed to put up an inclusive analysis of the OME proteome, establishing the first human OME proteome database. We focused on differential proteomic analysis among different groups to gain a more comprehensive concept of the OME proteome and search for meaningful biomarkers.

Dataset Information

Otitis media impacts hundreds of mouse middle and inner ear genes.

Objective

Methods

Results

Conclusion

Publications

Otitis media impacts hundreds of mouse middle and inner ear genes.

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