A life design model using mutator mice

• Project/Area Number: 15K14368
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Osaka University
• Principal Investigator: YAGI Takeshi 大阪大学, 生命機能研究科, 教授 (10241241)
• Co-Investigator(Renkei-kenkyūsha): UCHIMURA Arikuni 大阪大学, 大学院生命機能研究科, 助教 (20513063)
• Research Collaborator: HIGUCHI Mayumi
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 疾患モデル / マウス / 突然変異 / 量的形質 / DNA複製 / 生殖細胞 / ゲノム / 塩基配列 / 遺伝学 / 進化 / 多様性 / 生活習慣病

Outline of Final Research Achievements

In order to generate animal models for human diseases, we established mutator mouse strains which have high DNA replication error rates. We analyzed germline mutation rates and the long-term effects of mutation accumulation on phenotype in more than 20 generations of wild-type mice and mutator mice. We were successful to estimate the base-substitution mutation rate in C57BL/6 laboratory mice. The mutation rate in mutator mice was 17 times that in wild-type mice. As a result, we obtained phenotypes of human diseases from mutator mice.

Research Products

• [Journal Article] Clustered protocadherins are required for building functional neural circuits. (2017)
  • Author(s): Hasegawa S, Kobayashi H, Kumagai M, Nishimaru H, Tarusawa E, Kanda H, Kaneko R, Sanbo M, Yoshimura Y, Hirabayashi M, Hirabayashi T, Yagi T
  • Journal Title: Front Mol Neurosci Volume: 印刷中 Pages: 114-114
  • DOI: 10.3389/fnmol.2017.00114
  • Peer Reviewed / Open Access
• [Journal Article] Distinct and Cooperative Functions for the Protocadherin-alfa, -beta and -ganma Clusters in Neuronal Survival and Axon Targeting. (2016)
  • Author(s): Hasegawa S, Kumagai M, Hagiwara M, Nishimaru H, Hirano K, Kaneko R, Okayama A, Hirayama T, Sanbo M, Hirabayashi M, Watanabe M, Hirabayashi T, Yagi T
  • Journal Title: Front Mol Neurosci, Volume: 9 Pages: 155-155
  • DOI: 10.3389/fnmol.2016.00155
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins. (2016)
  • Author(s): Tarusawa E., Sanbo M., Okayama A., Miyashita T., Kitsukawa T., Hirayama T., Hirabayashi T., Hasegawa S., Kaneko R., Toyoda S., Kobayashi T., Kato-Itoh M., Nakauchi H., Hirabayashi M., Yagi T., Yoshimura Y.
  • Journal Title: BMC Biology Volume: 14 Issue: 1 Pages: 103-103
  • DOI: 10.1186/s12915-016-0326-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice (2015)
  • Author(s): Arikuni Uchimura, Mayumi Higuchi, Yohei Minakuchi, Mizuki Ohno, Atsushi Toyoda, Asao Fujiyama, Ikuo Miura, Shigeharu Wakana, Jo Nishino, Takeshi Yagi
  • Journal Title: Genome Research Volume: 25 Issue: 8 Pages: 1125-1134
  • DOI: 10.1101/gr.186148.114
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 生殖系列の変異率と変異蓄積マウス系統 (2015)
  • Author(s): 内村有邦
  • Journal Title: 実験医学 Volume: 33 Pages: 3123-3126
• [Journal Article] 集団遺伝学から考える脳の進化 (2015)
  • Author(s): 内村有邦、八木健
  • Journal Title: Clinical Neuroscience Volume: 33 Pages: 909-911
• [Presentation] Mutation accumulation experiment with laboratory mice (2017)
  • Author(s): Uchimura A,Yagi T
  • Organizer: International Symposium "The start of New Genomics"
  • Place of Presentation: 東京大学 伊藤国際学術研究センター（東京都文京区）
  • Year and Date: 2017-01-10
• [Presentation] マウスを用いた実験室内進化モデルは、ヒトも含めた哺乳類の進化研究に新たな方法論を提供する (2016)
  • Author(s): 内村有邦、樋口真弓、水口洋平、豊田敦、藤山秋佐夫、若菜茂晴、西野穣、八木健
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] 実験用マウスの生殖系列の突然変異率とその後世代への影響 (2016)
  • Author(s): 内村有邦、樋口真弓、水口洋平、豊田敦、藤山秋佐夫、若菜茂晴、西野穣、八木健
  • Organizer: 第63回日本実験動物学会総会
  • Place of Presentation: ミューザ川崎シンフォニーホール（神奈川県川崎市）
  • Year and Date: 2016-05-18
• [Presentation] Genetic codes for complex neural networks in the brain (2015)
  • Author(s): 八木 健
  • Organizer: Circuit Construction in the Mammalian Brain
  • Place of Presentation: 国立遺伝学研究所（静岡県三島市）
  • Year and Date: 2015-12-06
  • Int'l Joint Research / Invited
• [Presentation] Germline mutation rates and mutation accumulation lines in mice (2015)
  • Author(s): 内村 有邦
  • Organizer: 第29回国際哺乳類ゲノム会議
  • Place of Presentation: 横浜市開港記念会館（神奈川県横浜市）
  • Year and Date: 2015-11-08
  • Int'l Joint Research
• [Presentation] マウス変異蓄積統計を利用した生殖系列の突然変異率の推定 (2015)
  • Author(s): 内村 有邦
  • Organizer: 日本遺伝学会第87回大会
  • Place of Presentation: 東北大学 川内キャンパス内（宮城県仙台市）
  • Year and Date: 2015-09-24
• [Remarks] 阪大、突然変異マウスを高効率で誕生させることに成功
  • URL: http://www.zaikei.co.jp/article/20150906/267655.html
• [Remarks] 蓄積された突然変異が後世代に与える影響の解明に光
  • URL: http://www.fbs.osaka-u.ac.jp/jpn/events/achievement/uchimura-yagi-20150803/
• [Remarks] 心生物学研究室
  • URL: http://www.fbs.osaka-u.ac.jp/labs/yagi/index.htm