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Nonhuman model animal of Th2-mediated hyperimmune response 実績あり

外国特許コード F110005038
整理番号 A031-42US
掲載日 2011年8月18日
出願国 アメリカ合衆国
出願番号 49383502
公報番号 20050091703
公報番号 7301068
出願日 平成14年10月25日(2002.10.25)
公報発行日 平成17年4月28日(2005.4.28)
公報発行日 平成19年11月27日(2007.11.27)
国際出願番号 JP2002011105
国際公開番号 WO2003037079
国際出願日 平成14年10月25日(2002.10.25)
国際公開日 平成15年5月8日(2003.5.8)
優先権データ
  • 特願2001-331622 (2001.10.29) JP
  • 2002WO-JP11105 (2002.10.25) WO
発明の名称 (英語) Nonhuman model animal of Th2-mediated hyperimmune response 実績あり
発明の概要(英語) (US7301068)
An object of the present invention is to provide a nonhuman model animal of Th2-mediated hyperimmune response lacking PIR-B gene function on its chromosome by which the Th2-mediated immune response mechanism and allergy onset mechanism in vivo can be analyzed and which is liable to suffer from not only hyper-response of B cells but also allergy, and an inducer/promoter or an inhibitor for Th2-mediated immune response, etc. with the use of the nonhuman model animal of Th2-mediated hyperimmune response.
The nonhuman model animal of Th2-mediated hyperimmune response is prepared by integrating a fragment comprising exons 1 to 7 and the domain in the 5' side of exon 8 of mouse PIR-B gene and another fragment containing exons 10 to 14 into a vector pMC1-Neo, cleaving it with Xho I-Sal I, integrating it into a vector pIC19R-MC1tk having herpes virus thymidine kinase to thereby construct targeting vector, transferring the targeting vector into ES cells and then injecting the ES cells into blastcyst.
特許請求の範囲(英語) [claim1]
1. A transgenic mouse model of Th2-mediated hyperimmune response whose genome comprises a homozygous disruption of the PIR-B gene causing a loss of functional PIR-B expression, wherein said homozygous disruption facilitates a hyperimmune response of B cells.
[claim2]
2. The transgenic mouse model of Th2-mediated hyperimmune response according to claim 1, wherein said mouse develops a more severe immune response of B cells than a wild-type mouse by immunizing with an antigen that initiates Th2-mediated response.
[claim3]
3. The transgenic mouse model of Th2-mediated hyperimmune response according to claim 2, wherein the antigen that initiates the Th2-mediated response comprises an alum adjuvant, TNP-KLH and a pertussis toxin.
[claim4]
4. A method for screening an inducer/promoter or an inhibitor for Th2-mediated immune response or a promoter or an inhibitor for PIR-A function, wherein an alteration of Th2-mediated immune response or PIR-A function is determined after administering a test substance to the transgenic mouse model of Th2-mediated hyperimmune response according to claim 1 or contacting a tissue, an organ or cells comprising antigen presenting cells derived from the mouse to the test substance.
[claim5]
5. The method for screening an inducer/promoter or an inhibitor for Th2-mediated immune response or a promoter or an inhibitor for PIR-A function according to claim 4, wherein the alteration of Th2-mediated immune response is an alteration of activation of the B cell, generation of antibody, production of cytokine and/or antigen presentational ability in an antigen presenting cell.
[claim6]
6. The method for screening an inducer/promoter or an inhibitor for Th2-mediated immune response or a promoter or an inhibitor for PIR-A function according to claim 5, wherein the alteration of activation of the B cell is an alteration of development or proliferation of the B cell.
[claim7]
7. The method for screening an inducer/promoter or an inhibitor for Th2-mediated immune response or a promoter or an inhibitor for PIR-A function according to claim 5, wherein the alteration of generation of antibody is an alteration of generation of an IgM antibody, an IgG1 antibody, an IgG2b antibody and/or an IgG2a antibody.
[claim8]
8. The method for screening an inducer/promoter or an inhibitor for Th2-mediated immune response or a promoter or an inhibitor for PIR-A function according to claim 5, wherein the alteration of production of cytokine is an alteration of production of interleukin-4, IFN-gamma and/or interleukin-12.
[claim9]
9. The method for screening an inducer/promoter or an inhibitor for Th2-mediated immune response or a promoter or an inhibitor for PIR-A function according to claim 5, wherein the alteration of antigen presentational ability in the antigen presenting cell is an alteration of expression amount of a major histocompatibility complex class II, CD80and/or CD 86 in a dendritic cell.
[claim10]
10. The method for screening an inducer/promoter or an inhibitor for Th2-mediated immune response or a promoter or an inhibitor for PIR-A function according to claim 4, wherein the Th2-mediated hyperimmune response of said transgenic mouse model is further compared/evaluated with that of a wild type mouse.
[claim11]
11. The transgenic mouse model according to claim 1, wherein said transgenic mouse model has an impaired maturation of dendritic cells and a reduction in IL-12 compared to a wild-type mouse.
  • 発明者/出願人(英語)
  • TAKAI TOSHIYUKI
  • UJIKE-ASAI AZUSA
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
国際特許分類(IPC)
米国特許分類/主・副
  • 800/18
  • 800/3
  • 800/13
  • 800/21
参考情報 (研究プロジェクト等) CREST Host Defense Mechanism AREA
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