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Endotoxin-nonresponsive model animal 実績あり

外国特許コード F110003800
整理番号 E07202US
掲載日 2011年7月5日
出願国 アメリカ合衆国
出願番号 57321204
公報番号 20070143869
公報番号 7557258
出願日 平成16年9月29日(2004.9.29)
公報発行日 平成19年6月21日(2007.6.21)
公報発行日 平成21年7月7日(2009.7.7)
国際出願番号 JP2004014220
国際公開番号 WO2005030269
国際出願日 平成16年9月29日(2004.9.29)
国際公開日 平成17年4月7日(2005.4.7)
優先権データ
  • 特願2003-338013 (2003.9.29) JP
  • 2004WO-JP14220 (2004.9.29) WO
発明の名称 (英語) Endotoxin-nonresponsive model animal 実績あり
発明の概要(英語) (US7557258)
The present invention is to provide a non-human animal model non-responsive especially to endotoxin being a Gram-negative bacteria cell wall fraction, which is useful to elucidate the function of TIR domain-containing TRIF-related adaptor molecule (TRAM); and a method for screening substances promoting or suppressing responses to ligands recognized by TLR4 with the use of the non-human animal model non-responsive to endotoxin; and the like.
Mice non-responsive to the endotoxin wherein a part or a whole of Tram genes on their chromosome are deleted, the function to express TRAM which is expressed in wild-types is lacked, and the responsiveness to ligands recognized by TLR4 is specifically impaired; is used for screening substances promoting or suppressing responses to ligands recognized by TLR4.
特許請求の範囲(英語) [claim1]
1. A transgenic homozygous TRAM-knock out mouse non-responsive to endotoxin wherein a part or a whole of TRIF-related adaptor molecule (TRAM) genes on its chromosome is deleted, a function of expressing TRAM which is expressed in a wild-type is lacked, and responsiveness to a ligand recognized by TLR4 is specifically impaired.
[claim2]
2. The transgenic homozygous TRAM-knock out mouse non-responsive to endotoxin according to claim 1, which is responsive to PGN, R-848 and CpG ODN, and non-responsive to LPS.
[claim3]
3. A method for screening a substance promoting a response to a ligand recognized by TLR4, wherein a test substance is administered to an immunocyte derived from the knock out mouse of claim 1 or 2 and to an immunocyte derived from a wild-type mouse, and wherein the following responses (a) to (c) to the ligand recognized by TLR4 are measured: (a) cytokine (TNFalpha , IL-6 and IL-12p40) production of macrophage;
(b) splenocyte proliferation, and up-regulation of surface molecules; and
(c) expression of signaling molecules inducing IFN-beta production;
wherein a response for one or more of (a), (b), or (c) in the immunocyte derived from said wild-type mouse but not in the immunocyte derived from said knock out mouse indicates that the test substance promotes a response to a ligand recognized by TLR4.
[claim4]
4. A method for screening a substance promoting a response to a ligand recognized by TLR4, wherein a test substance is administered to the knock out mouse of claim 1 or 2 and to a wild-type mouse, and wherein the following responses (a) to (c) to the ligand recognized by TLR4 are measured: (a) cytokine (TNFalpha , IL-6 and IL-12p40) production of macrophage;
(b) splenocyte proliferation, and up-regulation of surface molecules; and
(c) expression of signaling molecules inducing IFN-beta production;
wherein a response for one or more of (a), (b), or (c) in said wild-type mouse but not in said knock out mouse indicates that the test substance promotes a response to a ligand recognized by TLR4.
[claim5]
5. An immunocyte from the transgenic homozygous TRAM-knock out mouse non-responsive to endotoxin according to claim 1 or 2.
  • 発明者/出願人(英語)
  • AKIRA SHIZUO
  • YAMAMOTO MASAHIRO
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
国際特許分類(IPC)
米国特許分類/主・副
  • A01K067/027M
  • G01N033/50D2J4
  • K01K217/05
  • K01K267/03
参考情報 (研究プロジェクト等) ERATO AKIRA Innate Immunity AREA
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