精巣における酸化ストレスによるアポトーシスの制御機構の解明

• Project/Area Number: 13J11021
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Research Field: Urology
• Research Institution: Osaka University (2014-2015); Kyoto University (2013)
• Principal Investigator: 奥田 英伸 大阪大学, 医学系研究科, 特別研究員(PD)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,960,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥660,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: Pgam5 / apoptosis / TRA98 / 男性不妊症 / Nkapl / Apoptosis / Meiosis / Notch signaling / TRA98 monoclonal antibody

Outline of Annual Research Achievements

Monash UniversityにてMoira O’Bryan教授の指導の下、主に２つのプロジェクトに取り組んでいる。
①精子形成におけるLRGUK1の機能：以前、当研究室ではLRGUK1のmutantマウスを樹立した。このマウスではアクロソーム、マンシェットの形成、精子の軸索形成異常が引き起こされる。そこでLrguk1の機能の解明を行うため、binding partnerの検索をYeast two hybridを用いて行った。Lrguk1の結合因子としていくらかの候補を確認したが、それらはいずれもtrans-Golgi networkからIntramanchette transport (IMT)の輸送にかかわる可能性の高い因子が得られた。現在それらの因子との結合に関して免疫沈降等を用いて解析しており、変異によりこれらの因子との結合に異常を生じているかについても調べている。
②Katnb1ノックアウトマウスの機能解析：KATNB1はmicrotubuleの切断・調節因子として働いており、精子形成においても多くの過程でmicrotubuleが関与している。KATNB1遺伝子はmicrotubuleの切断活性を調節する因子として機能していると考えられている。以前Katnb1 mutant mouseを当研究室で樹立した。Katnb1 mutant mouseではマンシェットの形成や軸索形成異常、さらに減数分裂時にapoptosisが著名に誘導されていた。そこで、Katnb1が減数分裂にどのようにかかわっているのかを解析している。Katnb1 conditional knockout mouseも樹立した。Katnb1 conditional knockout mouseではmutant mouseに比べてさらにsevereな表現型を認めた。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] A novel transcriptional factor Nkapl is a germ cell-specific suppressor of Notch signaling and is indispensable for spermatogenesis. (2015)
  • Author(s): Okuda H, Kiuchi, H, Takao,T, Tsujimura A, Nonomura N, Miyata H, Okabe M, Ikawa M, Kawakami Y, Goshima N, Wada M, Tanaka H
  • Journal Title: PLoS One. Volume: 14:10(4）
  • Peer Reviewed / Open Access
• [Journal Article] LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility. (2015)
  • Author(s): Liu Y, DeBoer K, de Kretser DM, O’Donnel L, O’Connor AE, Merriner DJ, Okuda, H, Whittle B, Jans D, Efthymiadis A, MacLachlan RI, Ormandy CJ, Goodnow CC, Jamsai D, O’Bryan MK
  • Journal Title: PLoS Genetics. Volume: 17:11(3）
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel transcriptional factor Nkapl is a germ cell-specific suppressor of Notch signaling and is indispensable for spermatogenesis. (2015)
  • Author(s): 1.Okuda H, Kiuchi, H, Takao,T, Tsujimura A, Nonomura N, Miyata H, Okabe M, Ikawa M, Kawakami Y, Goshima N, Wada M, Tanaka H
  • Journal Title: PLoS One Volume: in press Issue: 12 Pages: e15591-e15591
  • DOI: 10.1371/journal.pone.0015591
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility. (2015)
  • Author(s): 2.Liu Y, DeBoer K, de Kretser DM, O’Donnel L, O’Connor AE, Merriner DJ, Okuda, H, Whittle B, Jans D, Efthymiadis A, MacLachlan RI, Ormandy CJ, Goodnow CC, Jamsai D, O’Bryan MK
  • Journal Title: PLoS Genetics Volume: 11(3) Issue: 3 Pages: e1005090-e1005090
  • DOI: 10.1371/journal.pgen.1005090
  • Peer Reviewed / Open Access
• [Journal Article] Finger taps and constipation are closely related to symptoms of overactive bladder in male patients with Parkinson's disease. (2014)
  • Author(s): 3.Tsujimura A, Yamamoto Y, Sakoda S, Okuda H, Yamamoto K, Fukuhara S, Yoshioka I, Kiuchi H, Takao T, Miyagawa Y, Nonomura N
  • Journal Title: International Journal of Urology Volume: 21(8) Issue: 8 Pages: 821-5
  • DOI: 10.1111/iju.12429
  • Peer Reviewed
• [Journal Article] Sexual life of Japanese patients with erectile dysfunction taking phosphodiesterase type 5 inhibitors: an Internet survey using the Psychological and Interpersonal Relationship Scales-Short Form questionnaire. (2014)
  • Author(s): 4.Tsujimura A, Kiuchi H, Soda T, Takezawa K, Okuda H, Fukuhara S, Takao T, Nonomura N, Miyagawa Y
  • Journal Title: International Journal of Urology Volume: 21(1) Issue: 1 Pages: 69-73
  • DOI: 10.1111/iju.12186
  • Peer Reviewed
• [Journal Article] Standardized Diagram Improves Diagnostic Accuracy and Variability in the Identification of Testicular Cells Prepared for Testicular Sperm Extraction and Intracytoplasmic Sperm Injection. (2013)
  • Author(s): Okuda H, Tsujimura A, Kiuchi H, Matsuoka Y, Takao T, Takada S, Miyagawa Y, Tanaka H, Okamoto Y, Nonomura N.
  • Journal Title: Urology Volume: 82(3) Issue: 3 Pages: 594-594
  • DOI: 10.1016/j.urology.2013.05.023
  • Peer Reviewed
• [Journal Article] Correlation between overactive bladder symptoms and quality of life in Japanese male patients : focus on nocturia. (2013)
  • Author(s): Takao T, Tsujimura A, Kiuchi H, Takezawa K, Okuda H, Yamamoto K, Fukuhara S, Miyagawa Y, Nonomura N.
  • Journal Title: Urology Volume: 82(1) Issue: 1 Pages: 193-193
  • DOI: 10.1016/j.urology.2013.02.024
  • Peer Reviewed
• [Journal Article] Is low testosterone concentration a risk factor for metabolic syndrome in healthy middle-aged men? (2013)
  • Author(s): Tsujimura A, Miyagawa Y, Takezawa K, Okuda H, Fukuhara S, Kiuchi H, Takao T, Yamamoto R, Nishida M, Yamauchi-Takihara K, Moriyama T, Nonomura N.
  • Journal Title: Urology Volume: 82(4) Issue: 4 Pages: 819-819
  • DOI: 10.1016/j.urology.2013.06.023
  • Peer Reviewed
• [Presentation] “A novel transcription factor NKAPL is a germ cell-specific suppressor of the Notch signaling pathway and is indispensable for spermatogenesis”. (2015)
  • Author(s): Okuda Hidenobu
  • Organizer: The Annual scientific meeting of the Society for the Reproductive Biology in Adelaide.
  • Place of Presentation: Adelaide(Australia)
  • Year and Date: 2015-08-23
• [Presentation] Pgam5とKeap1-Nrf2制御系を中心とした環境応答による精細胞のアポトーシス機構の解明 (2013)
  • Author(s): 奥田 英伸
  • Organizer: 第63回日本泌尿器科学会中部総会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-11-30