a claudin-9–based ion permeability barrier is essential for hearingclaudin-9-based离子通透性屏障对听力至关重要.pdfVIP

A Claudin-9–Based Ion Permeability Barrier Is Essential for Hearing 1,2 3 3 3 4 Yoko Nakano , Sung H. Kim , Hyoung-Mi Kim , Joel D. Sanneman , Yuzhou Zhang , Richard J. H. 4 3 3 5 ´ 1,2,4,6 Smith , Daniel C. Marcus , Philine Wangemann , Randy A. Nessler , Botond Banfi * 1 Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, United States of America, 2 Inflammation Program, University of Iowa, Coralville, Iowa, United States of America, 3 Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas, United States of America, 4 Department of Otolaryngology – Head and Neck Surgery, University of Iowa, Iowa City, Iowa, United States of America, 5 Central Microscopy Research Facility, University of Iowa, Iowa City, Iowa, United States of America, 6 Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America Abstract Hereditary hearing loss is one of the most common birth defects, yet the majority of genes required for audition is thought to remain unidentified. Ethylnitrosourea (ENU)–mutagenesis has been a valuable approach for generating new animal models of deafness and discovering previously unrecognized gene functions. Here we report on the characterization of a new ENU–induced mouse mutant (nmf329) that exhibits recessively inherited deafness. We found a widespread loss of sensory hair cells in the hearing organs of nmf329 mice after the second week of life. Positional cloning revealed that the nmf329 strain carries a missense mutation in the claudin-9 gene, which encode