Depreux Frederic F S, Darrow Keith, Conner David A, Eavey Roland D, Liberman M Charles, Seidman Christine E, Seidman J G
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Clin Invest. 2008 Feb;118(2):651-8. doi: 10.1172/JCI32899.
Otitis media is an extremely common pediatric inflammation of the middle ear that often causes pain and diminishes hearing. Vulnerability to otitis media is due to eustachian tube dysfunction as well as other poorly understood factors, including genetic susceptibility. As EYA4 mutations cause sensorineural hearing loss in humans, we produced and characterized Eya4-deficient (Eya4(-/-)) mice, which had severe hearing deficits. In addition, all Eya4(-/-) mice developed otitis media with effusion. Anatomic studies revealed abnormal middle ear cavity and eustachian tube dysmorphology; thus, Eya4 regulation is critical for the development and function of these structures. We suggest that some human otitis media susceptibility reflects underlying genetic predisposition in genes like EYA4 that regulate middle ear and eustachian tube anatomy.
中耳炎是一种极其常见的小儿中耳炎症,常引起疼痛并导致听力下降。易患中耳炎是由于咽鼓管功能障碍以及其他一些尚未完全了解的因素,包括遗传易感性。由于EYA4突变会导致人类感音神经性听力损失,我们培育并鉴定了Eya4基因缺陷(Eya4(-/-))小鼠,这些小鼠存在严重的听力缺陷。此外,所有Eya4(-/-)小鼠都患上了渗出性中耳炎。解剖学研究显示中耳腔异常和咽鼓管形态异常;因此,Eya4的调控对于这些结构的发育和功能至关重要。我们认为,一些人类中耳炎易感性反映了EYA4等调节中耳和咽鼓管解剖结构的基因潜在的遗传易感性。