ゲノムネットワークプロジェクト

次世代ゲノム解析技術の開発
研究課題 精子幹細胞の遺伝子改変によるがん疾患モデルラットの作成
研究期間 平成18年度〜20年度
研究課題代表者 篠原 隆司
所属機関 京都大学大学院医学研究科
研究目的 従来の個体レベルの遺伝子改変は初期胚・卵子を中心にしているが、卵が脆弱であったり数が少ない動物に適用するのは困難であった。しかし、21世紀医学における「創薬・治療」というニーズを考えると、現在広く使われているマウスよりも、今後はよりヒトに近い疾患モデルを用いて研究していく必要がある。
研究概要 研究課題代表者が2003年に樹立したGermline Stem (GS)細胞は培養中で幹細胞として増殖し、精巣内に移植すると精子へと分化、子孫を作成する。今回の研究ではこのGS細胞の技術をラットに適用し、遺伝子ノックアウトによるがん疾患モデルラットの作成を試みる。
研究成果 これまでに数種類の系統のラットからGS細胞の樹立に成功し、これらのラットGS細胞をマウスへの異種移植により個体化することに成功した。また薬剤選択方法を確立し、遺伝子改変GS細胞および遺伝子改変個体の樹立を行なってきた。なお、本成果は Cell Stem Cell誌、PNAS誌等に掲載されるとともに、PNAS誌のNews にも取り上げられた。
データ種別 -
対象生物 ラット
組織・細胞株 ラット培養精子幹細胞(germlne stem cell)
対象遺伝子 -
実験情報 Glial cell line-derived neurotrophic factor, epidermal grwoth factor, fibroblast growth factorなどの増殖因子の存在下で培養を行い、ネオマイシンによる薬剤選択後、不妊マウスおよびラットの精細管内にマイクロインジェクションを行った。必要に応じて顕微授精を用いて精子からの遺伝子改変個体の作製を行った。
産出データ
全産出データのダウンロード(FTP)

(細胞名および遺伝子改変法)
XMLデータ -
研究論文・特許出願・
学術発表など
------------------------------ PATENT ------------------------------
PATENT ID: 242
APPLICANT:
APPLICATION DATE: 2007-10-25
APPLICATION NUMBER: 2006-290111
KOKAI DATE:
KOKAI NUMBER:
TITLE: 精原幹細胞のインビトロ増殖方法
STATUS: Filed
AUTHOR NAME: 篠原隆司、篠原美都
AUTHOR AFFILIATION: 京都大学

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:798
PUBLICATION TYPE: journal
PUBLICATION NAME: PNAS
ARTICLE TITLE: Rats produced by interspecies spermatogonial transplantation in mice and in vitro microinsemination.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2006-09-12
TITLE: Rats produced by interspecies spermatogonial transplantation in mice and in vitro microinsemination.
STATUS: Published
AUTHOR NAME: Shinohara T, Kato M, Takehashi M, Lee J, Chuma S, Nakatsuji N, Kanatsu-Shinohara M, Hirabayashi M.
AUTHOR AFFILIATION: Kyoto University, National Institute for Physiological Sciences

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:799
PUBLICATION TYPE: journal
PUBLICATION NAME: PNAS
ARTICLE TITLE: Adenovirus-mediated gene delivery into mouse spermatogonial stem cells.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-02-20
TITLE: Adenovirus-mediated gene delivery into mouse spermatogonial stem cells.
STATUS: Published
AUTHOR NAME: Takehashi M, Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, Toyokuni S, Ogura A, Shinohara T.
AUTHOR AFFILIATION: Kyoto University, RIKEN

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:800
PUBLICATION TYPE: journal
PUBLICATION NAME: Development
ARTICLE TITLE: Akt mediates self-renewal division of mouse spermatogonial stem cells.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-04-11
TITLE: Akt mediates self-renewal division of mouse spermatogonial stem cells.
STATUS: Published
AUTHOR NAME: Lee J, Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, Toyokuni S, Kimura T, Nakano T, Ogura A, Shinohara T.
AUTHOR AFFILIATION: Kyoto University, Osaka University, RIKEN

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1101
PUBLICATION TYPE: journal
PUBLICATION NAME: Developmental Biology
ARTICLE TITLE: Production of knockout mice by gene targeting in multipotent germline stem cells.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-09-28
TITLE: Production of knockout mice by gene targeting in multipotent germline stem cells.
STATUS: Published
AUTHOR NAME: Takehashi, M., Kanatsu-Shinohara, M., Miki, H., Lee, J., Kazuki, Y., Inoue, K., Ogonuki, N., Toyokuni, S., Oshimura, M., Ogura, A. and Shinohara, T.
AUTHOR AFFILIATION: Kyoto University, RIKEN BRC, Tottori University

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1102
PUBLICATION TYPE: Conference
PUBLICATION NAME: Keystone meeting (Stem cell interactions with microenvironmental niche)
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-03-06
TITLE: Culture and genetic modification of male germline stem (GS) cells.
STATUS: Presented
AUTHOR NAME: Takashi Shinohara
AUTHOR AFFILIATION: Kyoto University

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1103
PUBLICATION TYPE: Conference
PUBLICATION NAME: North American Testis Workshop
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-04-19
TITLE: Culture and genetic modification of germline stem (GS) cells.
STATUS: Presented
AUTHOR NAME: Takashi Shinohara
AUTHOR AFFILIATION: Kyoto University

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1104
PUBLICATION TYPE: Conference
PUBLICATION NAME: Mouse Molecular Genetics
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-09-06
TITLE: Culture and genetic modification of male germline stem (GS) cells.
STATUS: Presented
AUTHOR NAME: Takashi Shinohara
AUTHOR AFFILIATION: Kyoto University

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1105
PUBLICATION TYPE: Conference
PUBLICATION NAME: National Academy of Sciences colloquium
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-10-08
TITLE: Culture and genetic modification of male germline stem (GS) cells.
STATUS: Presented
AUTHOR NAME: Takashi Shinohara
AUTHOR AFFILIATION: Kyoto University

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1183
PUBLICATION TYPE: journal
PUBLICATION NAME: Biology of Reproduction
ARTICLE TITLE: Long-term culture of male germline stem cells from hamster testes
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-12-12
TITLE: Long-term culture of male germline stem cells from hamster testes
STATUS: Accepted
AUTHOR NAME: Mito Kanatsu-Shinohara, Tomomi Muneto, Jiyoung Lee, Manami Takenaka, Shinichiro Chuma, Norio Nakatsuji, Toshitaka Horiuchi, Takashi Shinohara
AUTHOR AFFILIATION: Kyoto University, Prefectural University of Hiroshima

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1184
PUBLICATION TYPE: journal
PUBLICATION NAME: Biology of Reproduction
ARTICLE TITLE: Pluripotency of a single spermatogonial stem cell in mice
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-12-12
TITLE: Pluripotency of a single spermatogonial stem cell in mice
STATUS: Accepted
AUTHOR NAME: Mito Kanatsu-Shinohara, Jiyoung Lee, Kimiko Inoue, Narumi Ogonuki, Hiromi Miki, Shinya Toyokuni, Masahito Ikawa, Tomoyuki Nakamura, Atsuo Ogura, Takashi Shinohara
AUTHOR AFFILIATION: Kyoto University, Osaka University, RIKEN BRC, Kansai Medical University

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1708
PUBLICATION TYPE: journal
PUBLICATION NAME: Biology of Reproduction
ARTICLE TITLE: Production of transgenic rats via Lentiviral Transduction and Xenogeneic Transplantation of Spermatogonial Stem Cells
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-08-06
TITLE: Production of transgenic rats via Lentiviral Transduction and Xenogeneic Transplantation of Spermatogonial Stem Cells
STATUS: Accepted
AUTHOR NAME: Kanatsu-Shinohara M, Kato M, Takehashi M, Morimoto H, Takashima S, Chuma S, Nakatsuji N, Hirabayashi M, Shinohara T
AUTHOR AFFILIATION: Kyoto University, National Institute of Physiology

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1709
PUBLICATION TYPE: journal
PUBLICATION NAME: Cell Stem Cell
ARTICLE TITLE: Homing of mouse spermatogonial stem cells to germline niche depends on β1-integrin.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-11-01
TITLE: Homing of mouse spermatogonial stem cells to germline niche depends on β1-integrin.
STATUS: Accepted
AUTHOR NAME: Kanatsu-Shinohara, M., Takehashi, M., Takashima, S., Lee, J., Chuma, S., Nakatsuji, N., Fässler R. Shinohara, T.
AUTHOR AFFILIATION: Kyoto University, Max Planch Institute of Biochemistry

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1710
PUBLICATION TYPE: journal
PUBLICATION NAME: Cold Spring Harb Symp Quant Biol
ARTICLE TITLE: Brief history, pitfalls, and prospects of mammalian spermatogonial stem cell research
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-12-01
TITLE: Brief history, pitfalls, and prospects of mammalian spermatogonial stem cell research
STATUS: Accepted
AUTHOR NAME: Mito Kanatsu-Shinohara, Masanori Takehashi, Takashi Shinohara
AUTHOR AFFILIATION: Kyoto University

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:2001
PUBLICATION TYPE: journal
PUBLICATION NAME: Biology of Reproduction
ARTICLE TITLE: Heritable imprinting defect caused by epigenetic abnormalities in mouse spermatogonial stem cells.
SUBMIT DATE: 2008-08-01
ACCEPT DATE: 2008-11-10
PUBLICATION DATE: 2009-03-01
TITLE: Heritable imprinting defect caused by epigenetic abnormalities in mouse spermatogonial stem cells.
STATUS: Accepted
AUTHOR NAME: Jiyong Lee, Mito Kanatsu-Shinohara, Narumi Ogonuki, Hiromi MIki, Kimiko Inoue, Takeshi Morimoto, Hiroko Morimoto, Atsuo Ogura, Takashi Shinohara
AUTHOR AFFILIATION: 京都大学、理研BRC

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:2002
PUBLICATION TYPE: journal
PUBLICATION NAME: Biology of Reproduction
ARTICLE TITLE: Abnormal DNA Methyltransferase Expression in Mouse Germline Stem Cells Results in Spermatogenic Defects
SUBMIT DATE: 2008-11-10
ACCEPT DATE: 2009-02-11
PUBLICATION DATE: 2009-06-01
TITLE: Abnormal DNA Methyltransferase Expression in Mouse Germline Stem Cells Results in Spermatogenic Defects
STATUS: Accepted
AUTHOR NAME: Takashima S, Takehashi M, Lee J, Chuma S, Okano M, Hata K, Suetake I, Nakatsuji N, Miyoshi H, Tajima S, Tanaka Y, Toyokuni S, Sasaki H, Kanatsu-Shinohara M, Shinohara T
AUTHOR AFFILIATION: 京都大学、国立遺伝学研究所、理研CDB, 成育医療センター、理研BRC, 名古屋大学、大阪大学

その他 2006年8月29日 京都新聞夕刊「「代理父」経由 ラットを出産 京大グループ」
2006年8月29日 日本経済新聞朝刊「ラットの精子 マウスで育てラット出産 京大 希少動物保存に応用も」
2006年8月29日 産経新聞夕刊「マウスからラットの子 精子幹細胞から正常な個体」
2006年8月29日 毎日新聞夕刊「異種間で精子移植 正常な子孫が誕生 京大グループ」
2006年8月29日 日刊工業新聞「マウス精巣でラット誕生 京大、畜産に応用期待」
2006年8月30日 ”National geographic news “Baby rats born from mice”
2006年9月1日  朝日新聞夕刊「マウスの精巣でラットの子誕生 京大グループが成功」
2007年2月14日 日本経済新聞「遺伝子治療のウイルス、精子幹細胞に感染、京大がマウス実験」
2008年11月6日 産経新聞「特殊タンパク質が精子形成に関与、男性不妊治療に道、京大チーム解明」
2008年12月1日 読売新聞「精子形成にタンパク質「インテグリン」関与、京大チーム解明」
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