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Nonhuman model animal unresponsive to immunopotentiating synthetic compound 実績あり

外国特許コード F110005238
整理番号 B02-01US
掲載日 2011年8月29日
出願国 アメリカ合衆国
出願番号 49650102
公報番号 20050235372
公報番号 7608750
出願日 平成14年11月22日(2002.11.22)
公報発行日 平成17年10月20日(2005.10.20)
公報発行日 平成21年10月27日(2009.10.27)
国際出願番号 JP2002012234
国際公開番号 WO2003043588
国際出願日 平成14年11月22日(2002.11.22)
国際公開日 平成15年5月30日(2003.5.30)
優先権データ
  • 特願2001-358295 (2001.11.22) JP
  • 2002WO-JP12234 (2002.11.22) WO
発明の名称 (英語) Nonhuman model animal unresponsive to immunopotentiating synthetic compound 実績あり
発明の概要(英語) (US7608750)
The present invention relates to provide a non-human animal model unresponsive to a synthetic compound wherein a gene function encoding TLR7 that recognizes an immunopotentiating synthetic compound such as imidazoquinoline lacks on is genomic locus.
Whole or part of a gene fragment of a gene site including an intracellular region and a transmembrane region of a TLR7 gene obtained from a mouse gene library is replaced by a plasmid including poly A signal and a marker gene to construct a targeting vector.
Then, this targeting vector is linearized and transferred into embryonic stem cells.
The target embryonic stem cells wherein the TLR7 gene function is deleted are microinjected into a mouse blastocyst to generate a chimeric mouse.
Then, this chimeric mouse is crossed with a wild-type mouse to generate a heterozygote mouse.
Next, the heterozygote mice are intercrossed to obtain a TLR7 knockout mouse.
特許請求の範囲(英語) [claim1]
1. A Toll-like receptor (TLR)7 homozygous knockout mouse whose genome comprises a disruption of a TLR7 gene, wherein the TLR7 homozygous knockout mouse lacks an increase of interferon-alpha compared with a wild-type mouse when R-848 is intraperitoneally injected into the mouse, and wherein a gene function that encodes TLR7 is deficient on its genomic locus.
[claim2]
2. The Toll-like receptor (TLR)7 homozygous knockout mouse according to claim 1, which is obtained by the following steps: (i) constructing a targeting vector by replacing whole or a part of a gene fragment of a gene site including an intracellular region and transmembrane region of a TLR7 gene obtained by screening a mouse gene library with a plasmid including a poly A signal and a marker gene; (ii) linearizing the targeting vector; (iii) introducing the linearized targeting vector into a mouse embryonic stem cell; (iv) microinjecting the targeted embryonic stem cell whose TLR7 gene function is deficient into a blastocyst of a mouse to generate a chimeric mouse; (v) intercrossing the chimeric mouse with a wild-type mouse to generate a heterozygote mouse; and (vi) intercrossing the heterozygote mouse.
[claim3]
3. The Toll-like receptor (TLR)7 homozygous knockout mouse according to claim 2, wherein the targeting vector comprises neomycin resistant gene as a marker and a diphtheria toxin A fragment (DT-A) gene or a herpes simplex virus thymidine kinase (HSV-tK) gene as a negative selection marker in 3'-terminal.
[claim4]
4. The Toll-like receptor (TLR)7 homozygous knockout mouse according to claim 2, wherein whole or a part of Toll-like receptor 7 gene is 1.8-kb TLR7 gene fragment encoding a part of leucine-rich repeat.
[claim5]
5. The Toll-like receptor (TLR)7 homozygous knockout mouse according to claim 4, wherein whole or a part of TLR7 gene is replaced with a neomycin resistant gene.
[claim6]
6. The Toll-like receptor (TLR)7 homozygous knockout mouse according to claim 5, wherein the neomycin resistant gene is pMC1 neo.
[claim7]
7. A method for producing a Toll-like receptor (TLR)7 homozygous knockout mouse whose genome comprises a disruption of a TLR7 gene, wherein the TLR7 homozygous knockout mouse lacks an increase of interferon-alpha compared with a wild-type mouse when R-848 is intraperitoneally injected into the mouse, the method comprising the following steps: (i) constructing a targeting vector by replacing whole or a part of a gene fragment of a gene site including an intracellular region and a transmembrane region of a TLR7 gene obtained by screening a mouse gene library with a plasmid including a poly A signal and a marker gene; (ii) linearizing the targeting vector; (iii) introducing the linearized targeting vector into a mouse embryonic stem cell; (iv) microinjecting the targeted embryonic stem cell whose TLR7 gene function is deficient into a blastocyst of a mouse to generate a chimeric mouse; (v) intercrossing the chimeric mouse with a wild-type mouse to generate a heterozygote mouse, and (vi) intercrossing the heterozygote mouse.
  • 発明者/出願人(英語)
  • AKIRA SHIZUO
  • TOMIZAWA HIDEYUKI
  • YAMAOKA TAKASHI
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
国際特許分類(IPC)
米国特許分類/主・副
  • 800/25
  • 800/13
  • 800/14
  • 800/18
参考情報 (研究プロジェクト等) SORST Selected in Fiscal 2000
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