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Model animals non-responsive to mycobacterial-origin lipoprotein/lipopeptide 実績あり

外国特許コード F110005239
整理番号 B02-02WO
掲載日 2011年8月29日
出願国 アメリカ合衆国
出願番号 51766302
公報番号 20060059579
公報番号 7329795
出願日 平成14年12月10日(2002.12.10)
公報発行日 平成18年3月16日(2006.3.16)
公報発行日 平成20年2月12日(2008.2.12)
国際出願番号 JP2002012908
国際公開番号 WO2003105578
国際出願日 平成14年12月10日(2002.12.10)
国際公開日 平成15年12月24日(2003.12.24)
優先権データ
  • 特願2002-173254 (2002.6.13) JP
  • 2002WO-JP12908 (2002.12.10) WO
発明の名称 (英語) Model animals non-responsive to mycobacterial-origin lipoprotein/lipopeptide 実績あり
発明の概要(英語) (US7329795)
The present invention is to provide TLR1 knockout mice specifically recognizing mycobacterial lipoproteins/lipopeptides, being useful to clarify the role of TLR1 in vivo, or a method for screening substances promoting or suppressing the response to mycobacterial lipoproteins/lipopeptides by using the same.
TLR1 genes are separated from murine genomic library, the genomic part containing the intracellular and transmembrane domain of the TLR1 gene is replaced with a neomycin resistant gene, HSV-tk gene being gene encoding thymidine kinase into 3' end is introduced, ES cell clones having double resistance to G418 and Gancyclovir are screened, and ES cell clones are injected into the blastocyst of C57BL/6 mice, to generate TLR1 knockout mice through the germline.
特許請求の範囲(英語) [claim1]
1. A transgenic mouse whose genome comprises a homozygous inactivation of the Toll-like Receptor 1 (TLR1) gene;
said TLR1 gene encoding a polypeptide that recognizes triacylated mycobacterial lipoproteins;
wherein peritoneal macrophages of the mouse, also comprising a homozygous inactivation of the TLR1 gene, exhibit decreased responsiveness to triacylated mycobacterial lipoproteins.
[claim2]
2. A method for screening substances that promote or suppres a response to triacylated mycobacterial lipoproteins comprising contacting peritoneal macrophages isolated from the transgenic TLR-1 inactivated mouse of claim 1, which exhibits a decreased responsiveness to triacylated mycobacterial lipoproteins, with a substance, contacting peritoneal macrophages isolated from a wild-type control mouse with said substance, and comparing the response between the TLR-1 inactivated peritoneal macrophages and the control macrophages, wherein an increase in said responsiveness in comparison to the control is indicative of a substance that promotes a response to a mycobacterial lipoprotein/lipopeptide in a TLR-1 independent manner and wherein a greater decrease in responsiveness to a mycobacterial lipoprotein/lipopeptide in comparison to a wild-type control mouse is indicative of a substance that inhibits a response to a mycobacterial lipoprotein/lipopeptide in a TLR-1 independent manner.
  • 発明者/出願人(英語)
  • AKIRA SHIZUO
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
国際特許分類(IPC)
米国特許分類/主・副
  • 800/18
  • 800/3
参考情報 (研究プロジェクト等) SORST Selected in Fiscal 2000
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