STAT1 deficiency predisposes to spontaneous otitis media
| Autor: | David Bächinger, Peter Kern, Daniel Bodmer, Soledad Levano Huaman, Arianne Monge Naldi |
|---|---|
| Přispěvatelé: | University of Zurich, Monsanto, Rafael da Costa, Levano Huaman, Soledad |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology Heredity Otology 10045 Clinic for Otorhinolaryngology Deafness Homozygosity Mice 0302 clinical medicine Medicine and Health Sciences STAT1 Immune Response Hearing Disorders Heterozygosity Multidisciplinary biology Genetically Modified Organisms General Medicine Cochlea STAT1 Transcription Factor medicine.anatomical_structure 030220 oncology & carcinogenesis Inner Ear Middle ear Engineering and Technology Medicine Anatomy medicine.symptom Genetic Engineering General Agricultural and Biological Sciences Research Article Biotechnology medicine.medical_specialty Science Immunology Ear Middle Bioengineering Inflammation 610 Medicine & health Genetics and Molecular Biology Proinflammatory cytokine 03 medical and health sciences Signs and Symptoms Ototoxicity Evoked Potentials Auditory Brain Stem Genetics medicine otorhinolaryngologic diseases Animals Inner ear 1000 Multidisciplinary Genetically Modified Animals business.industry Middle Ear Wild type Biology and Life Sciences medicine.disease Mice Inbred C57BL Otitis Media 030104 developmental biology Otitis Otorhinolaryngology Ears General Biochemistry biology.protein sense organs Clinical Medicine business Head |
| Zdroj: | PLoS ONE, Vol 15, Iss 9, p e0239952 (2020) PLoS ONE |
| Popis: | Signal transducer and activator of transcription 1 (STAT1) is known to be an important player in inflammatory responses. STAT1 as a transcription factor regulates the expression of multiple proinflammatory genes. Inflammatory response is one of the common effects of ototoxicity. Our group reported that hair cells of STAT1 knockout (STAT1-KO) mice are less sensitive to ototoxic agents in-vitro. The effect of inflammatory responses in STAT1-KO mice has primarily been studied challenging them with several pathogens and analyzing different organs of those mice. However, the effect of STAT1 ablation in the mouse inner ear has not been reported. Therefore, we evaluated the cochlear function of wild type and STAT1-KO mice via auditory brain stem response (ABR) and performed histopathologic analysis of their temporal bones. We found ABR responses were affected in STAT1-KO mice with cases of bilateral and unilateral hearing impairment. Histopathologic examination of the middle and inner ears showed bilateral and unilateral otitis media. Otitis media was characterized by effusion of middle and inner ear that varied between the mice in volume and inflammatory cell content. In addition, the thickness of the middle ear mucosae in STAT1-KO mice were more pronounced than those in wild type mice. The degree of middle and inner ear inflammation correlated with ABR threshold elevation in STAT1-KO mice. It appears that a number of mice with inflammation underwent spontaneous resolution. The ABR thresholds were variable and showed a tendency to increase in homozygous and heterozygous STAT1-KO mice. These findings suggest that STAT1 ablation confers an increased susceptibility to otitis media leading to hearing impairment. Thus, the study supports the new role of STAT1 as otitis media predisposition gene. |
| Databáze: | OpenAIRE |
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