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Method for genetically modified non human animal and complement dependent cell injury

机译:基因改性非人类动物和补体依赖性细胞损伤的方法

摘要

It relates to genetically modified non-human animals and immunodeficient non-human animals characterized by the recovery of complement-dependent cytotoxicity, and methods and compositions for evaluating therapeutic antibodies in genetically modified immunodeficient non-human animals. In certain embodiments, the present invention is immunodeficient non-obese diabetes (NOD), A / J, A / He, AKR, DBA / 2, NZB / B1N, B10.D2 / oSn, and other mouse strains. The present invention relates to a gene that has been genetically modified to restore complement-dependent cytotoxicity that is lacking in unmodified immunodeficient mice. In another specific embodiment, the present invention is, NOD.Cg-Prkdc scid IL2rg tmlWjl /SzJ(NSG),NOD.Cg-Rag1 tm1Mom Il2rg tmlWjl / SzJ (NRG), and NOD.Cg-Prkdcscid Il2rg tm1Sug / JicTac (NOG) relates to mice that have been genetically modified to restore complement-dependent cytotoxicity that is lacking in unmodified NSG, NRG, and NOG mice. Certain embodiments of the present invention provide methods for evaluating therapeutic or putative therapeutic antibodies in genetically modified immunodeficient mice characterized by an intact complement system.
机译:它涉及基因改性的非人动物和免疫缺陷非人类动物,其特征在于回收补体依赖性细胞毒性,以及用于评估遗传修饰的免疫缺乏非人动物中的治疗抗体的方法和组合物。在某些实施方案中,本发明是免疫缺乏非肥胖糖尿病(NOD),A / J,A / HE,AKR,DBA / 2,NZB / B1N,B10.D2 / OSN和其他小鼠菌株。本发明涉及遗传修饰以恢复依赖于未修饰的免疫缺陷小鼠的补体依赖性细胞毒性的基因。在另一个具体实施例中,本发明是,nod.cg-prkdc scid IL2rg tmlwjl / szj(nsg),nod.cg-rag1 tm1mom il2rg tmlwjl / szj(nrg)和 nod .cg-prkdc SCID IL2RG TM1SUG / JICTAC(NOG)涉及已遗传修饰的小鼠以恢复缺乏未修饰的NSG,NRG和NOG小鼠的补蛋白依赖性细胞毒性。本发明的某些实施方案提供了用于评估遗传修饰的免疫缺陷小鼠中的治疗或推定治疗性抗体的方法,其特征在于完整的补体系统。

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