Compound heterozygosity of the functionally null Cdh23v-ngt and hypomorphic Cdh23ahl alleles leads to early-onset progressive hearing loss in mice.

• Material Type: 博士論文
• Title: Compound heterozygosity of the functionally null Cdh23v-ngt and hypomorphic Cdh23ahl alleles leads to early-onset progressive hearing loss in mice.
• Author/Editor: Miyasaka, Yuki
• Publication, Distribution, etc.: 新潟大学
• Publication Date: 2016-03-23
• Publication Date (W3CDTF): 2016-03-23
• Alternative Title: Compound heterozygosity of the functionally null Cdh23v-ngt and hypomorphic Cdh23ahl alleles leads to early-onset progressive hearing loss in mice.; マウスにおけるカドヘリン23の機能欠損Cdh23v-ngtアレルとハイポモルフCdh23ahlアレルのヘテロ接合体は早発性・加齢性難聴を発症する
• Degree grantor/type: 新潟大学
• Date Granted: 2016-03-23
• Date Granted (W3CDTF): 2016-03-23
• Dissertation Number: 甲第4125号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第4125号
• Text Language Code: eng
• Subject Heading: age-related hearing loss; cadherin 23; hair cell; mouse mutant; stereocilia
• Note (General): The waltzer (v) mouse mutant harbors a mutation in Cadherin 23 (Cdh23) and is a model for Usher syndrome type 1D, which is characterized by congenital deafness, vestibular dysfunction, and prepubertal onset of progressive retinitis pigmentosa. In mice, functionally null Cdh23 mutations affect stereociliary morphogenesis and the polarity of both cochlear and vestibular hair cells. In contrast, the murine Cdh23^< ahl> allele, which harbors a hypomorphic mutation, causes an increase in susceptibility to age-related hearing loss in many inbred strains. We produced congenic mice by crossing mice carrying the v niigata (Cdh23^<v-ngt>) null allele with mice carrying the hypomorphic Cdh23^<ahl> allele on the C57BL/6J background, and we then analyzed the animals’ balance and hearing phenotypes. Although the Cdh23^<v-ngtlahl> compound heterozygous mice exhibited normal vestibular function, their hearing ability was abnormal: the mice exhibited higher thresholds of auditory brainstem response (ABR) and rapid age-dependent elevation of ABR thresholds compared with Cdh23^<ahllahl> homozygous mice. We found that the stereocilia developed normally but were progressively disrupted in Cdh23^<v-ngtlahl> mice. In hair cells, CDH23 localizes to the tip links of stereocilia, which are thought to gate the mechanoelectrical transduction channels in hair cells. We hypothesize that the reduction of Cdh23 gene dosage in Cdh23^<v-ngtlahl> mice leads to the degeneration of stereocilia, which consequently reduces tip link tension. These findings indicate that CDH23 plays an important role in the maintenance of tip links during the aging process.; 学位の種類: 博士（医学）. 報告番号: 甲第4125号. 学位記番号: 新大院博（医）甲第692号. 学位授与年月日: 平成28年3月23日; Experimental Animals. 2013, 62(4), 333-346.; 新大院博（医）甲第692号; 元資料の権利情報 : Copyright(C) 2013 Japanese Association for Laboratory Animal Science
• DOI: info:doi/10.1538/expanim.62.333; https://doi.org/info:doi/10.1538/expanim.62.333
• Persistent ID (NDL): info:ndljp/pid/9984817; https://dl.ndl.go.jp/pid/9984817
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• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2016-06-03T01:05:16+09:00
• Date Created (W3CDTF): 2019-08-05
• Format (IMT): application/pdf
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• Periodical Title (URI): http://hdl.handle.net/10191/41920
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp