Study of epigentic mechanism underlying age-related hearing loss

• Project/Area Number: 21791659
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: 独立行政法人国立病院機構東京医療センター(臨床研究センター) (2011); 独立行政法人国立病院機構(東京医療センター臨床研究センター) (2009-2010)
• Principal Investigator: MUTAI Hideki 独立行政法人国立病院機構東京医療センター(臨床研究センター), 聴覚平衡覚研究部, 研究員 (60415891)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 耳科学 / 神経科学 / 老化 / ゲノム / エピジェネティクス

Research Abstract

Auditory function is important for social communication. This study revealed evidence of epigenetic regulatory mechanism in rodent and primate auditory sensory epithelia. In DBA/2J, a mouse model of progressive/age-related hearing loss, several genes were found to change the genomic methylation levels as well as transcritpion levels in the auditory epithelium during progress of hearing loss. Treatment of the animals with drugs to modfy epigenetic mechanism successfully attenuated the progress of hearing loss.

Research Products

• [Journal Article] In silico Modeling of the Pore Region of a KCNQ4 Missense Mutant from a Patient with Hearing Loss (2012)
  • Author(s): Namba K, Mutai H, Kaneko H, Hashimoto S, Matsunaga T
  • Journal Title: BMC Research Notes Volume: 5 Pages: 145-145
• [Journal Article] A novel animal model of hearing loss caused by acute endoplasmic reticulum stress in the cochlea (2012)
  • Author(s): Fujinami Y, Mutai H, Mizutari K, Nakagawa S, and Matsunaga T
  • Journal Title: Journal of Pharmacological Sciences Volume: 118 Pages: 363-72
  • NAID: 10030455675
  • Peer Reviewed
• [Journal Article] In silico Modeling of the Pore Region of a KCNQ4 Missense Mutant from a Patient with Hearing Loss (2012)
  • Author(s): Namba K., Mutai H(equal contributor), et al
  • Journal Title: BMC Research Notes Volume: 5 Pages: 145-145
  • Peer Reviewed
• [Journal Article] Systematic analysis of mitochondrial genes associated with hearing loss in the Japanese population : dHPLC reveals a new candidate mutation (2011)
  • Author(s): Mutai H, Kouike H, Teruya E, Takahashi-Kodomoari I, Kakishima H, Taiji H, Usami S, Okuyama T and Matsunaga T
  • Journal Title: BMC Medical Genetics Volume: 12 Pages: 135-135
  • Peer Reviewed
• [Journal Article] Late-phase recovery in the cochlear lateral wall following severe degeneration by acute energy failure (2011)
  • Author(s): Mizutari K, Nakagawa S, Mutai H, Fujii M, Ogawa K, Matsunaga T
  • Journal Title: Brain Res Volume: 1419 Pages: 1-11
  • Peer Reviewed
• [Journal Article] Systematic analysis of mitochondrial genes associated with hearing loss in the Japanese population : dHPLC reveals a new candidate mutation (2011)
  • Author(s): Mutai H
  • Journal Title: BMC Medical Genetics Volume: 12 Pages: 135-135
  • Peer Reviewed
• [Journal Article] Enhanced expression of C/EBP homologous protein(CHOP) precedes degeneration of fibrocytes in the lateral wall after acute cochlear mitochondrial dysfunction induced by 3-nitropropionic acid (2010)
  • Author(s): Fujinami Y, Mutai H, Kamiya K, Mizutari K, Fujii M, Matsunaga T
  • Journal Title: Neurochemistry International Volume: 56 Pages: 487-494
  • Peer Reviewed
• [Journal Article] Enhanced expression of C/EBP homologous protein (CHOP) precedes degeneration of fibrocytes in the lateral wall after acute cochlear mitochondrial dysfunction induced by 3-nitropropionic acid. (2010)
  • Author(s): Yoshiaki Fujinami, ほか
  • Journal Title: Neurochemistry International 56 Pages: 487-494
  • Peer Reviewed
• [Journal Article] Promoted cell Proliferation by Connexin 30 Gene Transfection fo Head-and-Neck Cancer Cell Line (2009)
  • Author(s): Ozawa H, Mutai H, Tatsuo Matsunaga T, Tokumaru Y, Fujii M, Sakamoto K, Tomita T, Ogawa K
  • Journal Title: Anticancer Res Volume: 29 Pages: 1981-1986
  • Peer Reviewed
• [Journal Article] Expression of Pou3f3/Brn-1 and its genomic methylation in developing auditory epithelium (2009)
  • Author(s): Mutai H, Nagashima R, Sugitani Y, Noda T, Fujii M, Matsunaga T.
  • Journal Title: Develop. Neurobiol Volume: 69 Pages: 913-930
  • Peer Reviewed
• [Journal Article] Mitotic activity and specification of fibrocyte subtypes in the developing rat cochlear lateral wall (2009)
  • Author(s): Mutai H, Nagashima R, Fujii M, Matsunaga T
  • Journal Title: Neuroscience Volume: 163 Pages: 1255-1263
  • Peer Reviewed
• [Journal Article] Expression of Pou3f3/Brn-1 and its genomic methylation in developing auditory epithelium. (2009)
  • Author(s): Hideki Mutai, ほか
  • Journal Title: Developmental Neurobiology 69 Pages: 913-930
  • Peer Reviewed
• [Journal Article] Mitotic activity and specification of fibrocyte subtypes in the developing rat cochlear lateral wall. (2009)
  • Author(s): Hideki Mutai, ほか
  • Journal Title: Neuroscience 163 Pages: 1255-1263
  • Peer Reviewed
• [Presentation] Genotype and Phenotype Correlation in GJB2 Mutations(DFNB1) and Structural Analysis of Non-Inactivating Mutations (2012)
  • Author(s): Shujiro Minami, Kazunori Namba ; Hideki Mutai ; Tatsuo Matsunaga
  • Organizer: 第35回北米耳鼻咽喉科学会
  • Place of Presentation: サンディエゴ、米国
• [Presentation] dHPLC法を用いた日本人難聴者におけるミトコンドリア遺伝子多型解析 (2011)
  • Author(s): 務台英樹
  • Organizer: 第21回日本耳科学会
  • Place of Presentation: 沖縄コンベンションセンター
  • Year and Date: 2011-11-24
• [Presentation] 加齢性難聴動物モデルを用いたDNAメチル化解析 (2011)
  • Author(s): 務台英樹
  • Organizer: 第6回 感覚器センターシンポジウム
  • Place of Presentation: 東京医療センター
  • Year and Date: 2011-03-04
• [Presentation] Expression of DNA methyltransferases (Dnmts) in developing auditory epithelium and possible role for maintenance of hearing (2011)
  • Author(s): 務台英樹
  • Organizer: 第34回 北米耳鼻咽喉科学会
  • Place of Presentation: Marriot Waterfront Hotel, Baltimore, MA, USA
  • Year and Date: 2011-02-20
• [Presentation] dHPLC法を用いた日本人難聴者におけるミトコンドリア遺伝子多型解析 (2011)
  • Author(s): 務台英樹・泰地秀信、宇佐美真一、松永達雄
  • Organizer: 第21回日本耳科学会総会
  • Place of Presentation: 沖縄コンベンションセンター
• [Presentation] 温度感受性Auditory NeuropathyにおけるOTOF遺伝子の新規特異的変異の同定 (2011)
  • Author(s): 松永達雄、新正由紀子、山本聡、難波一徳、務台英樹、加我君孝
  • Organizer: 第21回日本耳科学会総会
  • Place of Presentation: 沖縄コンベンションセンター
• [Presentation] Expression of DNA methyltransferases(Dnmts) in developing auditory epithelium and possible role for maintenance of hearing (2011)
  • Author(s): Hideki Mutai, Susumu Nakagawa Kazunori Namba, Masato Fujii, Tatsuo Matsunaga
  • Organizer: 第34回北米耳鼻咽喉科学会
  • Place of Presentation: バルチモア米国
• [Presentation] 日本人小児Auditory Neuropathyの遺伝的要因の解明 (2010)
  • Author(s): 務台英樹
  • Organizer: 第55回人類遺伝学会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 2010-10-28
• [Presentation] 聴覚発達・老化と関連するDNAメチル化修飾とメチル化酵素Dnmt3a/3bの発現 (2010)
  • Author(s): 務台英樹
  • Organizer: 第20回日本耳科学会総会
  • Place of Presentation: 愛媛県・ひめぎんホール
  • Year and Date: 2010-10-08
• [Presentation] 新規変異型KCNQ4新規変異体蛋白質の立体構造情報による感音性難聴の検証 (2010)
  • Author(s): 難波一徳
  • Organizer: 第20回日本耳科学会総会
  • Place of Presentation: 愛媛県・ひめぎんホール
  • Year and Date: 2010-10-07
• [Presentation] 日本人小児Auditory Neuropathyの遺伝的要因の解明 (2010)
  • Author(s): 加我君孝
  • Organizer: 第20回日本耳科学会総会
  • Place of Presentation: 愛媛県・ひめぎんホール
  • Year and Date: 2010-10-07
• [Presentation] 発達中および成熟個体聴覚上皮におけるDNAメチル化酵素Dnmt3a/3bの発現 (2010)
  • Author(s): 務台英樹
  • Organizer: 第4回 日本エピジェネティクス研究会年会
  • Place of Presentation: 米子市文化ホール
  • Year and Date: 2010-05-28
• [Presentation] 聴覚発達とエピジェネティック制御機構 (2010)
  • Author(s): 務台英樹
  • Organizer: 第5回感覚器シンポジウム
  • Place of Presentation: 東京医療センター(東京都)
  • Year and Date: 2010-03-11
• [Presentation] 日本人小児Auditory NeuropathyにおけるOTOF遺伝子解析と治療法選択への活用 (2010)
  • Author(s): 松永達雄、國島伸治、務台英樹、難波一徳、加我君孝
  • Organizer: 第55回人類遺伝学会埼玉県さいたま市大宮区桜木町1-7-5
  • Place of Presentation: 大宮ソニックシティ
• [Presentation] 聴覚発達・老化と関連するDNAメチル化修飾とメチル化酵素Dnmt3a/3bの発現 (2010)
  • Author(s): 務台英樹・藤井正人・松永達雄
  • Organizer: 第20回日本耳科学会総会
  • Place of Presentation: 愛媛県ひめぎんホール
• [Presentation] 発達中および成熟個体聴覚上皮におけるDNAメチル化酵素Dnmt3a/3bの発現 (2010)
  • Author(s): 務台英樹、藤井正人、松永達雄
  • Organizer: 第4回日本エピジェネティクス研究会年会
  • Place of Presentation: 米子市文化ホール
• [Presentation] Expression of Pou3f3/Brn-1 and its genomic methylation in developing auditory epithelium (2009)
  • Author(s): 務台英樹, ほか
  • Organizer: 第32回日本分子生物学会年年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-09
• [Presentation] ラット蝸牛外側壁線維細胞の生後発達様式 (2009)
  • Author(s): 務台英樹, ほか
  • Organizer: 第32回日本耳科学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2009-10-08
• [Patent(Industrial Property Rights)] 難聴疾患の予防又は治療剤 (2011)
  • Inventor(s): 務台英樹、松永達雄、藤井正人
  • Industrial Property Rights Holder: 国立病院機構
  • Filing Date: 2011-01-18
• [Patent(Industrial Property Rights)] 難聴疾患の予防又は治療剤 (2011)
  • Inventor(s): 務台・藤井・松永
  • Industrial Property Rights Holder: 国立病院機構
  • Industrial Property Number: 2011-007581
  • Filing Date: 2011-01-18