Analysis of a novel hearing loss mechanism caused by mutated Cochlin

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14948
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: Yamamoto Kazoo 東京大学, 大学院新領域創成科学研究科, 教授 (20174782)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 遺伝性疾患 / 難聴 / cochlin / グリコサミノグリカン

Outline of Final Research Achievements

Several missense mutations in the gene encoding Cochlin have been identified in pedigrees afflicted with late-onset non-syndromic autosomal-dominant hearing loss 9 (DFNA9). In this study, we demonstrated that Cochlin binds to sulfated glycosaminoglycan (GAG) and compared GAG-binding ability among wild-type and mutated Cochlins. Furthermore, we established anti-Cochlin monoclonal antibodies and analyzed localization of Cochlin and Cochlin ligands in inner ear by using monoclonal antibodies and Cochlin-Fc protein. Together with the data of quantitative analysis of Cochlin ligands accompanying aging and of Cochlin proteolysis by metalloproteinase showed a possible mechanism for understanding autosomal-dominant late-onset hearing loss in DFNA9 patients.

Free Research Field

糖鎖生物学