In vivo gene function analysis using lentiviral vector

• Project/Area Number: 20670006
• Research Category: Grant-in-Aid for Young Scientists (S)
• Allocation Type: Single-year Grants
• Research Field: Laboratory animal science
• Research Institution: Osaka University
• Principal Investigator: IKAWA Masahito 大阪大学, 微生物病研究所, 教授 (20304066)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥96,850,000 (Direct Cost: ¥74,500,000、Indirect Cost: ¥22,350,000); Fiscal Year 2012: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000); Fiscal Year 2011: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000); Fiscal Year 2010: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000); Fiscal Year 2009: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000); Fiscal Year 2008: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
• Keywords: レンチウイルス / ジーントラップ / バイオリソース / 生殖 / 実験動物 / 不妊 / ノックアウト / 発生工学 / 疾患モデル / 胎盤 / 妊娠高血圧症候群

Research Abstract

In the present study, we developed the lentiviral vector system for random mutagenesis in mice. Next we analyzed reproductive failures found in the mice we created. Consequently, we found that genes coding testis specific proteins, Calr3, Pdilt, Tex101,and Pmis2are required for the maturation of sperm fertilizing protein, ADAM3, and male fertility. We further developed the preeclampsia model mice by placenta specific gene manipulation system.

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Research Products

• [Journal Article] Expression of TEX101, regulated by ACE, is essential for the production of fertile mouse spermatozoa (2013)
  • Author(s): FujiharaY, Tokuhiro K, Muro Y, Kondoh G, Araki Y, Ikawa M, Okabe M
  • Journal Title: PNAS Volume: 110(20) Issue: 20 Pages: 8111-6
  • DOI: 10.1073/pnas.1222166110
  • Peer Reviewed
• [Journal Article] A point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration (2013)
  • Author(s): Nojima S, et al.
  • Journal Title: Nat Commun Volume: 4 Issue: 1 Pages: 1406-1406
  • DOI: 10.1038/ncomms2420
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): Yamaguchi R, Fujihara Y, Ikawa M, Okabe M.Tokuhiro K, Ikawa M, Benham AM, Okabe M
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109 Issue: 10 Pages: 3850-5
  • DOI: 10.1073/pnas.1117963109
  • Peer Reviewed
• [Journal Article] SPACA1-deficient male mice are infertile with abnormally shaped sperm heads reminiscent of globozoospermia (2012)
  • Author(s): Fujihara Y, Satouh Y, Inoue N, Isotani A, Ikawa M, Okabe M
  • Journal Title: Development Volume: 139 Issue: 19 Pages: 3583-9
  • DOI: 10.1242/dev.081778
  • NAID: 120006957401
  • Peer Reviewed
• [Journal Article] Visualization of the moment of mouse sperm-egg fusion and dynamic localization of IZUMO1 (2012)
  • Author(s): Satouh Y, Inoue N, Ikawa M, Okabe M
  • Journal Title: Journal of Cell Science Volume: 125 Pages: 4985-4990
  • DOI: 10.1242/jcs.100867
  • NAID: 120006957400
  • Peer Reviewed
• [Journal Article] Mice expressing aberrant sperm-specific protein PMIS2 produce normal-looking but fertilization-incompetent spermatozoa (2012)
  • Journal Title: Mol Biol Cell Volume: 23 Issue: 14 Pages: 2671-9
  • DOI: 10.1091/mbc.e11-12-1025
  • Peer Reviewed
• [Journal Article] Neutrophil infiltration during inflammation is regulated by PILRalpha via modulation of integrin activation (2012)
  • Author(s): Wang J, et al.
  • Journal Title: Nat Immunol Volume: 14 Issue: 1 Pages: 2019-2025
  • DOI: 10.1038/ni.2456
  • Peer Reviewed
• [Journal Article] Production of mouse pups from germline transmission-failed knockout chimeras. (2012)
  • Author(s): Fujihara Y., et al.
  • Journal Title: Transgenic Res Volume: 22 Issue: 1 Pages: 195-200
  • DOI: 10.1007/s11248-012-9635-x
  • Peer Reviewed
• [Journal Article] GPHR-dependent functions of the Golgi apparatus are essential for the formation of lamellar granules and the skin (2012)
  • Author(s): Tarutani M, et al.
  • Journal Title: J Invest Dermatol Volume: 132 Issue: 8 Pages: 2019-2025
  • DOI: 10.1038/jid.2012.100
  • Peer Reviewed
• [Journal Article] Cold-inducible RNA-binding protein (Cirp) interacts with Dyrk1b/Mirk and promotes proliferation of immature male germ cells in mice (2012)
  • Author(s): Masuda T, et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Issue: 27 Pages: 10885-108901
  • DOI: 10.1073/pnas.1121524109
  • Peer Reviewed
• [Journal Article] Tetraspanin-interacting protein IGSF8 is dispensable for mouse fertility. (2012)
  • Author(s): Inoue N., et al.
  • Journal Title: Fertil Steril Volume: 98 Issue: 2 Pages: 465-470
  • DOI: 10.1016/j.fertnstert.2012.04.029
  • Peer Reviewed
• [Journal Article] Mice Deficient in Ficolin, a Lectin Complement Pathway Recognition Molecule, Are Susceptible to Streptococcus pneumoniae Infection (2012)
  • Author(s): Endo Y, et al.
  • Journal Title: J Immunol Volume: 189 Issue: 12 Pages: 5860-5866
  • DOI: 10.4049/jimmunol.1200836
  • Peer Reviewed
• [Journal Article] AMPD3-deficient mice exhibit increased erythrocyte ATP levels but anemia not improved due to PK deficiency (2012)
  • Author(s): Cheng J, et al.
  • Journal Title: Genes Cells Volume: 17 Issue: 11 Pages: 913-922
  • DOI: 10.1111/gtc.12006
  • Peer Reviewed
• [Journal Article] Characterization of inclusion bodies with cytoprotective properties formed by seipinopathy-linked mutant seipin (2012)
  • Author(s): Ito D, Yagi T, Ikawa M, Suzuki N
  • Journal Title: Human Molecular Genetics Volume: 21 Issue: 3 Pages: 635-46
  • DOI: 10.1093/hmg/ddr497
  • Peer Reviewed
• [Journal Article] Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model (2011)
  • Author(s): Kumasawa K, Ikawa M, Kidoya H, Hasuwa H, Saito-Fujita T, Morioka Y, Takakura N, Kimura T, Okabe M
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 Issue: 4 Pages: 1451-5
  • DOI: 10.1073/pnas.1011293108
  • Peer Reviewed
• [Journal Article] Calsperin Is a Testis-specific Chaperone Required for Sperm Fertility. (2011)
  • Author(s): Ikawa M*#, Tokuhiro K*, Yamaguchi R, Benham AM, Tamura T, Wada I, Satouh Y, Inoue N, Okabe M
  • Journal Title: J Biol Chem Volume: 286 Issue: 7 Pages: 5639-5646
  • DOI: 10.1074/jbc.m110.140152
  • Peer Reviewed
• [Journal Article] Acrosome-reacted mouse spermatozoa recovered from the perivitelline space can fertilize other eggs (2011)
  • Author(s): Inoue N, Satouh Y, Ikawa M, Okabe M, Yanagimachi R
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 Issue: 50 Pages: 20008-20011
  • DOI: 10.1073/pnas.1116965108
  • Peer Reviewed
• [Journal Article] Dynamic modification of sphingomyelin in lipid microdomains controls development of obesity, fatty liver, and type 2 diabetes (2011)
  • Author(s): Mitsutake S., et al
  • Journal Title: J Biol Chem Volume: 286 Issue: 32 Pages: 28544-55
  • DOI: 10.1074/jbc.m111.255646
  • Peer Reviewed
• [Journal Article] Homologous recombination in rat germline stem cells (2011)
  • Author(s): Kanatsu-Shinohara M., et al
  • Journal Title: Biol Reprod Volume: 85 Issue: 1 Pages: 208-17
  • DOI: 10.1095/biolreprod.111.090837
  • Peer Reviewed
• [Journal Article] Formation of a thymus from rat ES cells in xenogeneic nude mouse<--> rat ES chimeras (2011)
  • Author(s): Isotani A., et al
  • Journal Title: Genes Cells Volume: 16 Issue: 4 Pages: 397-405
  • DOI: 10.1111/j.1365-2443.2011.01495.x
  • Peer Reviewed
• [Journal Article] From the Cover : Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model. (2011)
  • Author(s): Kumasawa K*, Ikawa M*#, Kidoya H, Hasuwa H, Saito-Fujita T, Morioka Y, Takakura N, Kimura T, Okabe M.
  • Journal Title: Proc Natl Acad Sci USA 108 Pages: 1451-1455
  • Peer Reviewed
• [Journal Article] Calsperin Is a Testis-specific Chaperone Required for Sperm Fertility. (2011)
  • Author(s): Ikawa M*#, Tokuhiro K*, Yamaguchi R, Benham AM, Tamura T, Wada I, Satouh Y, Inoue N, Okabe M.
  • Journal Title: J Biol Chem 286 Pages: 5639-5646
  • Peer Reviewed
• [Journal Article] Fertilization: a sperm's journey to and interaction with the oocyte. (2010)
  • Author(s): Ikawa M, Inoue N, Benham AM, Okabe M#.
  • Journal Title: J Clin Invest Volume: 120 Issue: 4 Pages: 984-994
  • DOI: 10.1172/jci41585
  • Peer Reviewed
• [Journal Article] Fertilization : a sperm's journey to and interaction with the oocyte. (2010)
  • Author(s): Ikawa M, Inoue N, Benham AM, Okabe M#.
  • Journal Title: J Clin Invest 120 Pages: 984-994
  • Peer Reviewed
• [Journal Article] Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model (2010)
  • Author(s): Kumasawa K, et.al.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108(4) Pages: 1451-5
  • Peer Reviewed
• [Journal Article] Calsperin Is a Testis-specific Chaperone Required for Sperm Fertility (2010)
  • Author(s): Ikawa M, et.al.
  • Journal Title: J Biol Chem Volume: 286(7) Pages: 5639-46
  • Peer Reviewed
• [Journal Article] Fertilization : a sperm's journey to and interaction with the oocyte (2010)
  • Author(s): Ikawa M, et.al.
  • Journal Title: J Clin Invest Volume: 120(4) Pages: 984-94
  • Peer Reviewed
• [Journal Article] Placenta-specific gene activation and inactivation using integrase-defective lentiviral vectors with the Cre/LoxP system (2009)
  • Author(s): Morioka Y, Isotani A, Oshima RG, Okabe M, Ikawa M#
  • Journal Title: Genesis Volume: 47 Issue: 12 Pages: 793-798
  • DOI: 10.1002/dvg.20563
  • Peer Reviewed
• [Journal Article] Targeted gene modification in mouse ES cells using integrase-defective lentiviral vectors. (2009)
  • Author(s): Okada Y, Ueshin Y, Hasuwa H, Takumi K, Okabe M, Ikawa M#
  • Journal Title: Genesis Volume: 47 Issue: 4 Pages: 217-223
  • DOI: 10.1002/dvg.20469
  • Peer Reviewed
• [Journal Article] Placenta-specific gene activation and inactivation using integrase-defective lentiviral vectors with the Cre/LoxP system (2009)
  • Author(s): Morioka Y, Isotani A, Oshima RG, Okabe M, Ikawa M#.
  • Journal Title: Genesis 47 Pages: 793-798
  • Peer Reviewed
• [Journal Article] Targeted gene modification in mouse ES cells using integrase-defective lentiviral vectors. (2009)
  • Author(s): Okada Y, Ueshin Y, Hasuwa H, Takumi K, Okabe M, Ikawa M#.
  • Journal Title: Genesis 47 Pages: 217-223
  • Peer Reviewed
• [Journal Article] Targeted gene modification in mouse ES cells using integrase-defective lentiviral vectors (2009)
  • Author(s): Okada, Y. et. al.
  • Journal Title: Genesis (in press)
  • Peer Reviewed
• [Journal Article] Putative sperm fusion protein IZUMO and the role of N-glycosylation. (2008)
  • Author(s): Inoue, N. et. al.
  • Journal Title: Biochem Biophys Res Commun 377 Pages: 910-4
  • Peer Reviewed
• [Journal Article] Cd52, known as a major maturation-associated sperm membrane antigen secreted from the epididymis, is not required for fertilization in the mouse. (2008)
  • Author(s): Yamaguchi, R. et. al.
  • Journal Title: Genes Cells 13 Pages: 335-45
  • Peer Reviewed
• [Journal Article] Mechanisms of sperm-egg interactions emerging from gene-manipulated animals. (2008)
  • Author(s): Ikawa, M. et. al.
  • Journal Title: Int J Dev Biol 52 Pages: 657-64
  • Peer Reviewed
• [Presentation] ER chaperones, ADAM3, and sperm fertilizing ability (2013)
  • Author(s): 伊川正人
  • Organizer: 日本発生生物学会第46回大会
  • Place of Presentation: 松江
  • Year and Date: 2013-05-31
• [Presentation] 遺伝子改変動物を用いた生殖メカニズムの解明 (2013)
  • Author(s): 伊川正人
  • Organizer: 第1回実験動物科学シンポジウム
  • Place of Presentation: 京都大学 百周年時計台記念館(招待講演)
  • Year and Date: 2013-02-01
• [Presentation] 小胞体シャペロンと精子受精能力 (2012)
  • Author(s): 伊川正人
  • Organizer: 関西生殖発生毒性フォーラム
  • Place of Presentation: 大阪市立弁天町市民学習センター(招待講演)
  • Year and Date: 2012-11-10
• [Presentation] Placental Gene Manipulation and Its Application in the Study of Placental Biology and Diseases (2012)
  • Author(s): Masahito Ikawa
  • Place of Presentation: 北京, China
  • Year and Date: 2012-05-10
• [Presentation] Placental Gene Manipulation and Its Application in the Study of Placental Biology and Diseases (2012)
  • Author(s): Masahito Ikawa
  • Organizer: The 2nd SKLRB Symposia on Frontiers in Reproductive Biology
  • Place of Presentation: Beijing Xijiao Hotel 中国(招待講演)
  • Year and Date: 2012-05-10
• [Presentation] ANZPLA meeting (satellite meeting of WCRB) (2011)
  • Author(s): Masahito Ikawa
  • Organizer: Lentiviral transduction & placenta-specific gene manipulation to study PE in a mouse model
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2011-10-07
• [Presentation] Lentiviral transduction & placenta-specific gene manipulation to study PE in a mouse model (2011)
  • Author(s): Masahito Ikawa
  • Organizer: World Congress on Reproductive Biology
  • Place of Presentation: Cairns, Australia(招待講演)
  • Year and Date: 2011-10-07
• [Presentation] (2011)
  • Author(s): Masahito Ikawa
  • Organizer: 9th International Calreticulin Workshop
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2011-08-29
• [Presentation] Testis specific calreticulin homologue, calsperin, regulates sperm fertility (2011)
  • Author(s): Masahito Ikawa
  • Organizer: 9th International Calreticulin Workshop
  • Place of Presentation: Copenhagen, Denmark(招待講演)
  • Year and Date: 2011-08-29
• [Presentation] 胎盤の遺伝子操作とその応用 (2011)
  • Author(s): 伊川正人
  • Organizer: 第58回日本実験動物学会総会
  • Place of Presentation: 船堀
  • Year and Date: 2011-05-25
• [Presentation] 胎盤の遺伝子操作とその応用 (2011)
  • Author(s): 伊川正人
  • Organizer: 第58回日本実験動物学会総会
  • Place of Presentation: 船堀(招待講演)
  • Year and Date: 2011-05-25
• [Presentation] Lentiviral vector mediated gene transfer and its application in mouse genetics. (2010)
  • Author(s): Masahito Ikawa
  • Organizer: The 4^<th> AFLAS Congress meeting.
  • Place of Presentation: Taipei
  • Year and Date: 2010-11-11
• [Presentation] Lentiviral vector mediated gene transfer and its application in mouse genetics (2010)
  • Author(s): Masahito Ikawa
  • Organizer: The 4th AFLAS Congress meeting
  • Place of Presentation: 台湾台北市 Taipei International Convention Center(中華民国)(招待講演)
  • Year and Date: 2010-11-11
• [Presentation] Lentiviral vector mediated gene transfer and its application in mouse genetics (2010)
  • Author(s): Masahito Ikawa
  • Organizer: Asian Federation of Laboratory Animal Science Associations Annual Meeting
  • Place of Presentation: Taipei, 中華民国
  • Year and Date: 2010-11-09
• [Presentation] Placenta specific gene manipulation using lentiviral vectors (2009)
  • Author(s): Masahito Ikawa
  • Organizer: 4th Asian Mouse Mutagenesis Resource Association meeting
  • Place of Presentation: Singapore
  • Year and Date: 2009-12-17
• [Presentation] Placenta specific gene manipulation using lentiviral vectors. (2009)
  • Author(s): Masahito ikawa
  • Organizer: 4^<th> AMMRA meeting
  • Place of Presentation: Kumamoto
  • Year and Date: 2009-12-17
• [Presentation] 精巣シャペロンが制御する精子の受精能力 (2009)
  • Author(s): 伊川正人
  • Organizer: 第80回日本動物学会
  • Place of Presentation: 静岡
  • Year and Date: 2009-09-17
• [Presentation] レンチウイルスベクターを用いた新しいジーントラップ法の開発 (2009)
  • Author(s): 伊川正人
  • Organizer: 第56回日本実験動物学会総会
  • Place of Presentation: 大宮
  • Year and Date: 2009-05-15
• [Presentation] ER Chaperones and Sperm Fertility. (2009)
  • Author(s): Masahito Ikawa
  • Organizer: Keystone Symposia (Frontiers in Reproductive Biology and Regulation of Fertility)
  • Place of Presentation: Santa Fe
  • Year and Date: 2009-02-01
• [Presentation] ウイルスベクターを用いた胎盤特異的な遺伝子機能解析 (2008)
  • Author(s): 伊川正人
  • Organizer: 日本生殖医学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-10-23
• [Book] 発明者および扶桑薬品 (2010)
  • Author(s): 妊娠高血圧症候群モデル動物とその治療方法
  • Total Pages: 20100304
  • Publisher: 岡部勝、伊川正人、木村正、熊澤恵一
• [Remarks]
  • URL: http://www.egr.biken.osaka-u.ac.jp/information/
• [Remarks]
  • URL: http://www.arcid.biken.osaka-u.ac.jp/index.php
• [Remarks]
  • URL: http://www.egr.biken.osaka-u.ac.jp/
• [Remarks]
  • URL: http://www.egr.biken.osaka-u.ac.jp/
• [Remarks]
  • URL: http://kumikae01.gen-info.osaka-u.ac.jp/members/ikawa/index.htm
• [Patent(Industrial Property Rights)] 栄養外胚葉細胞特異的遺伝子導入法 (2012)
  • Inventor(s): 岡部勝、伊川正人
  • Industrial Property Rights Holder: 岡部勝、伊川正人
  • Acquisition Date: 2012-06-22
• [Patent(Industrial Property Rights)] 妊娠高血圧症候群モデル動物とその治療方法 (2010)
  • Inventor(s): 伊川正人、熊澤恵一、木村正、岡部勝
  • Industrial Property Rights Holder: 発明者および扶桑薬品工業
  • Industrial Property Number: 2010-048237
  • Filing Date: 2010-03-04