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Mouse models for human otitis media.

ABSTRACT: Otitis media (OM) remains the most common childhood disease and its annual costs exceed $5 billion. Its potential for permanent hearing impairment also emphasizes the need to better understand and manage this disease. The pathogenesis of OM is multifactorial and includes infectious pathogens, anatomy, immunologic status, genetic predisposition, and environment. Recent progress in mouse model development is helping to elucidate the respective roles of these factors and to significantly contribute toward efforts of OM prevention and control. Genetic predisposition is recognized as an important factor in OM and increasing numbers of mouse models are helping to uncover the potential genetic bases for human OM. Furthermore, the completion of the mouse genome sequence has offered a powerful set of tools for investigating gene function and is generating a rich resource of mouse mutants for studying the genetic factors underlying OM.

SUBMITTER: Trune DR

PROVIDER: S-EPMC2832702 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Mouse models for human otitis media.

Trune Dennis R DR Zheng Qing Yin QY

Brain research 20090306

Otitis media (OM) remains the most common childhood disease and its annual costs exceed $5 billion. Its potential for permanent hearing impairment also emphasizes the need to better understand and manage this disease. The pathogenesis of OM is multifactorial and includes infectious pathogens, anatomy, immunologic status, genetic predisposition, and environment. Recent progress in mouse model development is helping to elucidate the respective roles of these factors and to significantly contribute ...[more]

PMID: 19272362

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A defect in early myogenesis causes Otitis media in two mouse models of 22q11.2 Deletion Syndrome.

Project description:Otitis media (OM), the inflammation of the middle ear, is the most common disease and cause for surgery in infants worldwide. Chronic Otitis media with effusion (OME) often leads to conductive hearing loss and is a common feature of a number of craniofacial syndromes, such as 22q11.2 Deletion Syndrome (22q11.2DS). OM is more common in children because the more horizontal position of the Eustachian tube (ET) in infants limits or delays clearance of middle ear effusions. Some mouse models with OM have shown alterations in the morphology and angle of the ET. Here, we present a novel mechanism in which OM is caused not by a defect in the ET itself but in the muscles that control its function. Our results show that in two mouse models of 22q11.2DS (Df1/+ and Tbx1(+/-)) presenting with bi- or unilateral OME, the fourth pharyngeal arch-derived levator veli palatini muscles were hypoplastic, which was associated with an earlier altered pattern of MyoD expression. Importantly, in mice with unilateral OME, the side with the inflammation was associated with significantly smaller muscles than the contralateral unaffected ear. Functional tests examining ET patency confirmed a reduced clearing ability in the heterozygous mice. Our findings are also of clinical relevance as targeting hypoplastic muscles might present a novel preventative measure for reducing the high rates of OM in 22q11.2DS patients.

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Otitis media metagenome

Project description:Impact of narrow-spectrum antibiotics on the oral and fecal microbiome and resistome in a young child treated for otitis media

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Otitis Media Impact on Ear

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-07-23 | GSE49129 | GEO

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

Project description:ObjectiveOtitis 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.MethodsTo 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.ResultsStatistical 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.ConclusionWhole 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.

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Otitis Media Impact on Middle Ear

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.

2013-07-23 | GSE49128 | GEO

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2013-07-23 | GSE49122 | GEO

Acute Otitis Media Curriculum.

Project description:IntroductionStudies have shown that clinicians do a poor job of diagnosing middle ear infections, and an inaccurate diagnosis may result in inappropriate treatment, such as overuse of antibiotics. Antibiotic overuse is known to lead to increased bacterial resistance and puts patients at risk of deleterious side effects, including allergic reactions, vomiting, diarrhea, and rash. In this curriculum, we teach three important topics for achieving a successful middle ear exam and diagnosis of pathology.MethodsThe topics covered during the session are middle ear examination techniques, diagnosis of middle ear pathology and criteria for diagnosing acute otitis media, and treatment of acute otitis media. Each topic has a 30-minute lesson plan with broad goals, specific and measurable learning objectives, interactive learning activities, and assessment measures. Teaching activities include a mix of knowledge, skill, and attitude activities. Assessment measures aim at the highest level of Miller's pyramid of assessment when possible. Also included is a scholarship map that relates how this learning activity can fit into the assessment of learners at the program level by linking learning objectives with pediatric developmental milestones.ResultsThe interactive nature of these lessons has been very well received by learners, and pediatric residents have had a self-perceived increase in skills.DiscussionThis curriculum provides a standardized approach to teaching the middle ear exam structured by educational rubrics and allows for accurate assessment of learners.

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Increased susceptibility to otitis media in a Splunc1-deficient mouse model.

Project description:Otitis media (inflammation of the middle ear) is one of the most common diseases of early childhood. Susceptibility to otitis is influenced by a number of factors, including the actions of innate immune molecules secreted by the epithelia lining the nasopharynx, middle ear and Eustachian tube. The SPLUNC1 (short palate, lung, nasal epithelial clone 1) protein is a highly abundant secretory product of the mammalian nasal, oral and respiratory mucosa that is thought to play a multifunctional role in host defense. In this study we investigated Splunc1 expression in the ear of the mouse, and examined whether this protein contributes to overall host defense in the middle ear and/or Eustachian tube. We found that Splunc1 is highly expressed in both the surface epithelium and in submucosal glands in these regions in wild-type mice. In mice lacking Splunc1, we noted histologically an increased frequency of otitis media, characterized by the accumulation of leukocytes (neutrophils with scattered macrophages), proteinaceous fluid and mucus in the middle ear lumens. Furthermore, many of these mice had extensive remodeling of the middle ear wall, suggesting a chronic course of disease. From these observations, we conclude that loss of Splunc1 predisposes mice to the development of otitis media. The Splunc1(-/-) mouse model should help investigators to better understand both the biological role of Splunc1 as well as host defense mechanisms in the middle ear.

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Influenza-induced inflammation drives pneumococcal otitis media

Project description:Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes. Here, we demonstrate that the viral hemagglutinin (HA) mediates bacterial OM by inducing a pro-inflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings show that it is the inflammatory response that mediates pneumococcal replication; not viral suppression of the immune system or epithelial damage. This study provide the first evidence that HA induced inflammation drives pneumococcal replication in the middle ear cavity, which has important consequences to the treatment of pneumococcal OM.

2013-01-01 | GSE41098 | GEO

Nystagmus in adult patients with acute otitis media or otitis media with effusion without dizziness.

Project description:The present study aimed to investigate the incidence and patterns of nystagmus in adult patients with acute otitis media (AOM) or otitis media with effusion (OME) without dizziness or vertigo, and discuss possible mechanisms. From February 2018 to November 2018, 34 consecutive patients with AOM or OME without dizziness were included. Nystagmus was examined with video Frenzel glasses. Of 34 adult AOM or OME patients without dizziness, nystagmus was observed in 28 patients (82%). In unilateral AOM or OME (n = 30), the most commonly observed nystagmus pattern was irritative-type direction-fixed nystagmus (n = 13), followed by paretic-type direction-fixed nystagmus (n = 8), and direction-changing positional nystagmus (n = 4). In bilateral AOM or OME (n = 4), direction-fixed nystagmus and direction-changing positional nystagmus were observed in two and one patients, respectively. Nystagmus was observed in as many as 82% of adult AOM or OME patients even though they did not complain of dizziness, and the pattern of nystagmus was either direction-fixed or direction-changing. Direct effect of inflammatory mediators penetrated from the middle ear and biochemical alteration in the inner ear fluids due to blood-perilymph barrier dysfunction may result in the presence of nystagmus in AOM or OME patients without dizziness.

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