Mechanism of inner ear development revealed from PAX2 heterozygous gene abnormality

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09864
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kanazawa University
• Principal Investigator: Sugimoto Hisashi 金沢大学, 医学系, 准教授 (20547179)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: PAX2

Outline of Final Research Achievements

We checked the patients with renal coloboma syndrome in our hospital, 3 out of 7 patients showed sensorineural hearing loss in the high frequency range despite being relatively young. And all three cases had a heterogeneous mutation of PAX2. From these results, it was clarified that the PAX heterogeneous gene abnormality may cause sensorineural hearing loss in the high frequency range. However, no significant difference was found in the elucidation of the cause of hearing loss from both cochlear malformation and histological analysis of the organ of Corti, and in the verification of inner ear vulnerability using ototoxic drugs.

Free Research Field

耳科学

Academic Significance and Societal Importance of the Research Achievements

PAX2は眼，中枢神経および尿生殖器(腎，尿管，性器)の発生過程に関与し，その異常は同部位の形態・機能異常の原因となることが知られている。聴覚器の発生にかかわる遺伝子をも制御するため、その異常により感音難聴などの感覚器の先天異常を引き起こす。今回の研究はPAX２のヘテロ遺伝子異常により発症する腎コロボーマ症候群患者の内耳生理機能と形態異常を分析し、同時にPAX２ヘテロノックアウトマウスの聴覚器異常およびその脆弱性について解析したはじめての試みである。