Analysis on genetic and environmental factors using a mouse model for dominantly inherited disease

• Project/Area Number: 17200028
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kumamoto University
• Principal Investigator: YAMAMURA Kenichi Kumamoto University, 発生医学研究センター, 教授 (90115197)
• Co-Investigator(Kenkyū-buntansha): KAWAKAMI Minoru 熊本大学, 発生医学研究センター, 助教 (40363527)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥48,360,000 (Direct Cost: ¥37,200,000、Indirect Cost: ¥11,160,000); Fiscal Year 2008: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000); Fiscal Year 2007: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000); Fiscal Year 2006: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2005: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
• Keywords: トランスサイレチン / アミロイドポリニューロパチー / 相同組換え / キメラ / 野生マウス / ES 細胞 / 遺伝子破壊マウス / ES細胞 / ヒト化マウス / ノックアウトマウス / 可変型相同組換え / ノックアヴトマウス

Research Abstract

家族性アミロイドポリニューロパチーは優性遺伝病であり、トランスサイレチン(TTR)遺伝子の異常によって発症する。その病因・病態解析を行うため、マウスTTR 遺伝子をヒト正常TTR遺伝子及びヒト変異TTR 遺伝子で置換したマウスの作製に成功した。また、病原微生物がいない環境でモデルマウスを飼育すると全く発症しないことを明らかにした。また、日本産野生マウス由来のMSM/Ms からのES 細胞の樹立に成功した。

Research Products

• [Journal Article] International gene trap project : Towards gene-driven saturation mutagenesis in mice (2009)
  • Author(s): Araki, M., Araki, K. and Yamamura, K.
  • Journal Title: Current Pharmaceutical Biothechnology 10 Pages: 221-229
  • Peer Reviewed
• [Journal Article] Establishment of germline-competent embryonic stem cell lines from the MSM/Ms strain (2009)
  • Author(s): Araki, K., 他7名
  • Journal Title: Mammal. Genome 20 Pages: 14-20
  • Peer Reviewed
• [Journal Article] A role for ornithine decarboxylase antizyme inhibitor in vivo (2009)
  • Author(s): Tang, H., et al.
  • Journal Title: Genes Cells 14 Pages: 79-87
  • Peer Reviewed
• [Journal Article] Inconsistency between hepatic expression and serum concentration of transthyretin in mice humanized at the transthyretin locus (2008)
  • Author(s): Zhao, G. 他8名
  • Journal Title: Genes Cells 13 Pages: 1257-1268
  • Peer Reviewed
• [Journal Article] Specific pathogen free conditions prevents transthyretin amyloidosis in mouse models (2008)
  • Author(s): Inoue, S.他12名
  • Journal Title: Transgenic Res. 17 Pages: 817-826
  • Peer Reviewed
• [Journal Article] Expression pattern of the serine protease inhibitor Kazal Type 3 (Spink3)gene during the mouse embryonic development (2008)
  • Author(s): Wang, J.他5名
  • Journal Title: Histochem. Cell Biol 130 Pages: 387-397
  • Peer Reviewed
• [Journal Article] Cranial bone morphometric study among mouse strains (2008)
  • Author(s): Kawakami, M. and Yamamura, K.
  • Journal Title: BMC(BioMed Central)Evolutionary Biol 8 Pages: 73-83
  • Peer Reviewed
• [Journal Article] Gene trap mutagenesis in mice ; New perspectives and tools in cancer research (2008)
  • Author(s): Yamamura, K. and Araki, K.
  • Journal Title: Cancer Science 99 Pages: 1-6
  • NAID: 10024000620
  • Peer Reviewed
• [Journal Article] Specific pathogen free conditions prevents transthyretin amyloidosis in mouse models. (2008)
  • Author(s): Inoue, S., et al.
  • Journal Title: Transgenic Res. 17 Pages: 817-826
  • Peer Reviewed
• [Journal Article] Inconsistency between hepatic expression and serum concentration of transthyretin in mice humanized at the transthyretin locus. (2008)
  • Author(s): Zhao, G.
  • Journal Title: Genes Cells 13 Pages: 1257-1268
  • Peer Reviewed
• [Journal Article] Establishment of germline-competent embryonic stem cell lines from the MSM/Ms strain. (2008)
  • Author(s): Araki, K., et al.
  • Journal Title: Mammal. Genome 20 Pages: 14-20
  • Peer Reviewed
• [Journal Article] Early pre-implantion lethality in mice carrying truncated mutation in the RNA polymerase 1-2 gene. (2008)
  • Author(s): Chen, H., et. al.
  • Journal Title: Biochem.Biophys.Res.Commun 365 Pages: 636-642
  • Peer Reviewed
• [Journal Article] Methy-Beta-cyclodextrin improves fertilizing ability of C57BL/6 mouse sperm after freezing and thawing by facilitating cholesterol efflux from the cells. (2008)
  • Author(s): Takeo, T., et. al.
  • Journal Title: Biol.Reprod (In press)
  • Peer Reviewed
• [Journal Article] Characterization of Ayu17-449 gene expression and resultant kidney pathology in a knockout mouse model. (2008)
  • Author(s): Tang, H., et. al.
  • Journal Title: Transgenic Res. (In press)
  • Peer Reviewed
• [Journal Article] Efficient conversion of ES cells into myogenic lineage using the gene-inducible system. (2007)
  • Author(s): Ozasa, S., et. al.
  • Journal Title: Biochem.Biophys.Res.Commun. 359 Pages: 957-963
  • Peer Reviewed
• [Journal Article] LGR4 regulates the postnatal development and integrity of male reproductive tracts in mice. (2007)
  • Author(s): Hoshii, T.et al.
  • Journal Title: Biol.Reprod. 76 Pages: 303-313
• [Journal Article] Meltrin b expression in cardiac neural crest cells is required for ventricular septum formation of the heart (2007)
  • Author(s): Komatsu, K.et al.
  • Journal Title: Dev.Biol. 303 Pages: 82-92
• [Journal Article] Negative Selection with the Diphtheria toxin A fragment Gene Improves Frequency of Cre-Mediated Cassette Exchange in ES Cells (2006)
  • Author(s): Araki, K., Araki, M. and Yamamura, K.
  • Journal Title: J. Biochem. 140 Pages: 793-798
  • NAID: 10018840450
  • Peer Reviewed
• [Journal Article] Immunization in familial amyloidotic polyneuropathy : counteracting deposition by immunization with a Y78F TTR mutant (2006)
  • Author(s): Terazaki, H.他5名
  • Journal Title: Lab. Invest 86 Pages: 23-31
  • Peer Reviewed
• [Journal Article] Impaired expression of Importin/karyopherin β 1 leads to post - implantation lethality (2006)
  • Author(s): Miura, K., 他10名
  • Journal Title: Biochem. Biophys. Res. Commun 341 Pages: 132-138
  • Peer Reviewed
• [Journal Article] Negative Selection with the Diphtheria toxin A fragment Gene Improves Frequency of Cre-Mediated Cassette Exchange in ES Cells. (2006)
  • Author(s): Araki, K.et al.
  • Journal Title: J.Biochem. 140 Pages: 793-798
• [Journal Article] Abnormal migration and distribution of neural crest cells in Pax6 heterozygous mutant eye, a model for human eye diseases. (2006)
  • Author(s): Kanakubo, S.et al.
  • Journal Title: Genes to Cells 11 Pages: 919-933
• [Journal Article] Enhanced trypsin activity in pancreatic acinar cells deficient for serine protease inhibitor Kazal type 3 (2006)
  • Author(s): Ohmuraya, M.et al.
  • Journal Title: Pancreas 33 Pages: 104-106
• [Journal Article] Smooth muscle-specoific dystrophin expression improves aberrant vasoregulation in mdx mice. (2006)
  • Author(s): Ito, K.et al.
  • Journal Title: Human Mol.Genet. 152 Pages: 2266-2275
• [Journal Article] Impaired expression of Importin/karyopherin β1 leads to post-implantation lethality. (2006)
  • Author(s): Miura, K. et al.
  • Journal Title: Biochem Biophys Res Commun. 341 Pages: 132-138
• [Journal Article] The international gene trap consortium web site : a portal to all publly available gene trap cell lines and mouse. (2006)
  • Author(s): Nord, A.S.et al.
  • Journal Title: Nucleic Acids Res. 34
• [Journal Article] A novel murine gene, Sickle tail(Skt), linked to the Danforth's short tail(Sd) locus, is required for normal development of the intervertebral disc. (2006)
  • Author(s): Semba, K. et al.
  • Journal Title: Genetics 172 Pages: 445-456
• [Journal Article] Characterization of an exchangeable gene trap using pU-17 carrying a stop codon-betageo cassette. Dev (2005)
  • Author(s): Taniwaki, T. 他13名
  • Journal Title: Growth Differ 47 Pages: 163-172
  • Peer Reviewed
• [Journal Article] Animal model of occulopharyngeal muscular dystrophy. (2005)
  • Author(s): Uyama, E. et al.
  • Journal Title: Acta Myologica XXIV Pages: 84-88
• [Journal Article] Presence and distribution of neural crest-derived cells in the murine developing thymus and their potential for differentiation. (2005)
  • Author(s): Yamazaki, H. et al.
  • Journal Title: Int.Immunol. 17 Pages: 549-558
• [Journal Article] Sonic hedgehog is required for cardiac outflow tract and neural crest cell development. (2005)
  • Author(s): Washington Smoaka, I. et al.
  • Journal Title: Dev.Biol. 283 Pages: 357-372
• [Presentation] ヒト疾患の遺伝学的解析のためのモデルマウス(シンポジウム) (2008)
  • Author(s): 山村研一
  • Organizer: 日本人類遺伝学会第53回大会
  • Place of Presentation: 横浜
• [Presentation] Establishment of embryonic stem cell lines derived from MSM/Ms strain originated from Mus musculus molossinus., (2008)
  • Author(s): Araki, K. et.al.
  • Organizer: 41^<st> Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: 徳島
• [Presentation] MSM/Ms 系統からの生殖系列キメラが高率に得られるES 細胞株の樹立 (2008)
  • Author(s): 荒木喜美他
  • Organizer: 日本実験動物科学技術2008
  • Place of Presentation: 仙台
• [Presentation] Role of Spink3 in autophagy regulation and induction of pancreatitis (2008)
  • Author(s): Yamamura, K.
  • Organizer: 11^<th> International Symposium on Molecular Medicine
  • Place of Presentation: Crete island, Greece
• [Presentation] Knock-in human TTR gene into mouse Ttr locus by Cre-loxP system for the a mouse model of ATTR (2007)
  • Author(s): 趙 綱, 他
  • Organizer: 第24回日本疾患モデル学会総会
  • Place of Presentation: つくば
  • Year and Date: 2007-08-31
• [Presentation] MSM/Ms 及びJF1/Ms 系統からのES 細胞株の樹立 (2007)
  • Author(s): 荒木喜美他
  • Organizer: 第30 回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] ESTABLISHMENT OF EMBRYONIC STEM CELL LINES DERIVED FROM MSM/MS STRAIN ORIGINATED FROM MUS MUSCULUS MOLOSSINUS (2007)
  • Author(s): Araki, K. et.al.
  • Organizer: 21^<st> International Mammalian Genome Conference IMGC2007
  • Place of Presentation: 京都
• [Presentation] ヒト疾患研究における動物モデルの有用性と世界の現状(教育講演) (2007)
  • Author(s): 山村研一
  • Organizer: 第52 回大会日本人類遺伝学会
  • Place of Presentation: 東京
• [Presentation] Knock-in human TTR gene into mouse Ttr locus by Cre-loxP system for the a mouse model of ATTR (2007)
  • Author(s): 趙綱他
  • Organizer: 第24 回日本疾患モデル学会総会
  • Place of Presentation: つくば
• [Presentation] 世界のノックアウトプロジェクト(シンポジウム) (2007)
  • Author(s): 山村研一
  • Organizer: 第24 回日本疾患モデル学会総会
  • Place of Presentation: つくば
• [Presentation] ES 細胞においてlox71 部位に対して良い組換え効率を示す新たなRE 変異loxの探索 (2007)
  • Author(s): 荒木喜美他
  • Organizer: 第40 回日本発生生物学会・第59 回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] C57BL/6N 由来ES 細胞RENKA株の核型解析について (2007)
  • Author(s): 藤田恒久他
  • Organizer: 第54 回日本実験動物学会総会
  • Place of Presentation: 東京
• [Presentation] ヒト疾患研究における動物モデルの有用性と世界の現状 (2007)
  • Author(s): 山村 研一
  • Organizer: 第52回大会日本人類遺伝学会
  • Place of Presentation: 東京
• [Presentation] ESTABLISHMENT OF EMBRYONIC STEM CELL LINES DERIVED FROM MSM/MS STRAIN ORエGエNATED FROM MUS MUSCULUS MOLOSSINUS (2007)
  • Author(s): Araki, et. al.
  • Organizer: 21st International Mammalian Genome Conference
  • Place of Presentation: Kyoto
• [Presentation] ポストゲノムにおける遺伝子改変動物の役割 (2006)
  • Author(s): 山村研一
  • Organizer: 教育セミナーフォーラム2006テーマ「実験動物及び畜産分野におけるトランスジェニック技術」(遺伝子組換え技術入門)
  • Place of Presentation: 東京
  • Year and Date: 2006-03-25
• [Presentation] Gene-environment Interactions in Mammalian Development and Disease (2006)
  • Author(s): Yamamura, K.
  • Organizer: The 22^<nd> International Kumamoto Medical Bioscience Symposium
  • Place of Presentation: Kumamoto
• [Presentation] 優性遺伝病マウスモデルおよび大規模疾患モデル開発 (2006)
  • Author(s): 山村研一
  • Organizer: 日本人類遺伝学会第51回大会The 51th Annual Meeting of the Japan Society of Human Genetics
  • Place of Presentation: 米子
• [Presentation] ポストゲノムにおける疾患モデルの意義 (2006)
  • Author(s): 山村研一
  • Organizer: 第3 回日本病理学会カンファレンス日本病理学会カンファレンス2006 東京「疾患モデルの命題ー本質を見極めるー」
  • Place of Presentation: 東京
• [Presentation] MSM/Ms 由来のES 細胞の樹立とノックアウトプロジェクト (2006)
  • Author(s): 山村研一
  • Organizer: 平成17年度国立遺伝学研究所研究会第20 回モノシヌス研究会
  • Place of Presentation: 熱海
• [Presentation] Negative selection with the DT-A gene improves frequency of Cre-mediated cassette exchange in ES cells (2006)
  • Author(s): Araki,K. et.al.
  • Organizer: 日本発生生物学会第39 回大会
  • Place of Presentation: 広島
• [Presentation] C57BL/6 由来ES 細胞株RENKAを用いた遺伝子破壊マウスの作製について (2006)
  • Author(s): 中務胞他
  • Organizer: 第53 回日本実験動物学会総会
  • Place of Presentation: 神戸
• [Presentation] ヒト疾患の解析における新しいマウスモデル (2006)
  • Author(s): 山村研一
  • Organizer: 第3 回日本癌学会カンファレンス動物モデルによる新時代のがん研究発症機構から治療まで
  • Place of Presentation: 長野
• [Presentation] 可変型遺伝子トラップクローンのβ geo/EGFP 遺伝子置換で見られた表現型の変化 (2005)
  • Author(s): 荒木正健他
  • Organizer: 第28 回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] Feeder-free TT2 ES 細胞を用いた可変型遺伝子トラップによる変異マウスライン樹立 (2005)
  • Author(s): 春名享子他
  • Organizer: 第28 回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] Post-insertional engineering of trapped alleles using site-specific recombination in exchangeable trap clones (2005)
  • Author(s): Araki, M. et.al.
  • Organizer: International Symposium on Germ Cells, Epigenetcs, Reprogramming and Embryonic Stem Cells
  • Place of Presentation: 京都
• [Presentation] ヒト疾患モデルの大規模作製 (2005)
  • Author(s): 山村研一
  • Organizer: 日本人類遺伝学会第50 回大会
  • Place of Presentation: 岡山
• [Presentation] ヘテロ接合体の掛け合わせで得られた胚盤胞の培養によるホモ接合体ES 細胞の効率的樹立 (2005)
  • Author(s): 荒木喜美他
  • Organizer: 第38 回日本発生生物学会
  • Place of Presentation: 仙台
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/divisions/developmental_genetics/index.html
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/