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公开(公告)号：US08871996B2
公开(公告)日：2014-10-28
申请号：US13155491
申请日：2011-06-08
IPC分类号： A01K67/027
CPC分类号： A01K67/0278 , A01K2217/072 , A01K2227/105 , A01K2267/0356
摘要： Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a humanization of an extracellular loop of an endogenous NaV channel gene, in particular a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein. Genetically modified non-human animals are also provided, wherein the genetic modification comprises replacement of an endogenous NaV channel gene, in particular a replacement of the endogenous NaV1.7 gene with a human NaV1.7 gene, and wherein the genetically modified non-human animals are capable of generating action potentials and communicating through the excitable cells of the genetically modified non-human animals via the expressed human or humanized NaV1.7 protein the surface of the excitable cells. Genetically modified mice are described, including mice that express the human or humanized NaV1.7 gene from the endogenous NaV1.7 locus, and wherein the mice comprise functional β-subunits.
摘要翻译： 提供了遗传修饰的非人动物以及用于制备和使用它们的方法和组合物，其中所述遗传修饰包括内源性NaV通道基因的细胞外环的人源化，特别是一种或多种细胞外孔环的人源化 NaV1.7通道蛋白。 还提供了遗传修饰的非人动物，其中遗传修饰包括内源性NaV通道基因的替换，特别是用人NaV1.7基因替代内源性NaV1.7基因，并且其中所述遗传修饰的非人动物 动物能够通过表达的人或人源化NaV1.7蛋白质产生动力电位并通过基因修饰的非人动物的可兴奋细胞进行通信，所述可激活细胞的表面。 描述了转基因小鼠，包括从内源性NaV1.7基因座表达人或人源化NaV1.7基因的小鼠，其中小鼠包含功能性和亚基。
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公开(公告)号：US20120083000A1
公开(公告)日：2012-04-05
申请号：US13236117
申请日：2011-09-19
IPC分类号： G01N33/567
CPC分类号： C07K14/435
摘要： Methods and compositions for using genetically modified non-human animals are provided, wherein the genetic modification comprises a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein or a complete humanization of an endogenous NaV1.7 gene. Methods for using isolated DRG cultures from genetically modified non-human animals are also provided, wherein the isolated DRG express a human or chimeric NaV1.7 protein on the surface, in particular measuring primary nociceptive activation through the release of calcitonin gene-related peptide (CGRP) in isolated DRG in vitro, and wherein the isolated DRG cultures are capable of generating action potentials and communicating through an excitable signal via the expressed human or chimeric NaV1.7 protein the cell surface. In vivo and in vitro methods for characterizing NaV1.7-specific antagonists and evaluation of corresponding therapeutic potential for NaV1.7-mediated disease are also provided.
摘要翻译： 提供了使用遗传修饰的非人动物的方法和组合物，其中遗传修饰包括NaV1.7通道蛋白的一个或多个胞外孔环的人源化或内源性NaV1.7基因的完全人源化。 还提供了使用来自遗传修饰的非人动物的分离的DRG培养物的方法，其中分离的DRG在表面上表达人或嵌合的NaV1.7蛋白，特别是通过释放降钙素基因相关肽测量初级伤害感受激活（ CGRP），其中分离的DRG培养物能够产生动作电位并通过表达的人或嵌合的NaV1.7蛋白的细胞表面通过可兴奋的信号传递。 还提供了用于表征NaV1.7特异性拮抗剂的体内和体外方法以及对NaV1.7介导的疾病的相应治疗潜力的评估。
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公开(公告)号：US20110307966A1
公开(公告)日：2011-12-15
申请号：US13155491
申请日：2011-06-08
IPC分类号： A01K67/027 , C12N15/63 , C12N5/10
CPC分类号： A01K67/0278 , A01K2217/072 , A01K2227/105 , A01K2267/0356
摘要： Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a humanization of an extracellular loop of an endogenous NaV channel gene, in particular a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein. Genetically modified non-human animals are also provided, wherein the genetic modification comprises replacement of an endogenous NaV channel gene, in particular a replacement of the endogenous NaV1.7 gene with a human NaV1.7 gene, and wherein the genetically modified non-human animals are capable of generating action potentials and communicating through the excitable cells of the genetically modified non-human animals via the expressed human or humanized NaV1.7 protein the surface of the excitable cells. Genetically modified mice are described, including mice that express the human or humanized NaV1.7 gene from the endogenous NaV1.7 locus, and wherein the mice comprise functional β-subunits.
摘要翻译： 提供了遗传修饰的非人动物以及用于制备和使用它们的方法和组合物，其中所述遗传修饰包括内源性NaV通道基因的细胞外环的人源化，特别是一种或多种细胞外孔环的人源化 NaV1.7通道蛋白。 还提供了遗传修饰的非人动物，其中遗传修饰包括内源性NaV通道基因的替换，特别是用人NaV1.7基因替代内源性NaV1.7基因，并且其中所述遗传修饰的非人动物 动物能够通过表达的人或人源化NaV1.7蛋白质产生动力电位并通过基因修饰的非人动物的可兴奋细胞进行通信，所述可激活细胞的表面。 描述了转基因小鼠，包括从内源性NaV1.7基因座表达人或人源化NaV1.7基因的小鼠，其中小鼠包含功能性和亚基。
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公开(公告)号：US08486647B2
公开(公告)日：2013-07-16
申请号：US13236117
申请日：2011-09-19
IPC分类号： C07K14/705 , C07K19/00 , C12N15/62 , G01N33/567
CPC分类号： C07K14/435
摘要： Methods and compositions for using genetically modified non-human animals are provided, wherein the genetic modification comprises a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein or a complete humanization of an endogenous NaV1.7 gene. Methods for using isolated DRG cultures from genetically modified non-human animals are also provided, wherein the isolated DRG express a human or chimeric NaV1.7 protein on the surface, in particular measuring primary nociceptive activation through the release of calcitonin gene-related peptide (CGRP) in isolated DRG in vitro, and wherein the isolated DRG cultures are capable of generating action potentials and communicating through an excitable signal via the expressed human or chimeric NaV1.7 protein the cell surface. In vivo and in vitro methods for characterizing NaV1.7-specific antagonists and evaluation of corresponding therapeutic potential for NaV1.7-mediated disease are also provided.
摘要翻译： 提供了使用遗传修饰的非人动物的方法和组合物，其中遗传修饰包括NaV1.7通道蛋白的一个或多个胞外孔环的人源化或内源性NaV1.7基因的完全人源化。 还提供了使用来自遗传修饰的非人动物的分离的DRG培养物的方法，其中分离的DRG在表面上表达人或嵌合的NaV1.7蛋白，特别是通过释放降钙素基因相关肽测量初级伤害感受激活（ CGRP），其中分离的DRG培养物能够产生动作电位并通过表达的人或嵌合的NaV1.7蛋白的细胞表面通过可兴奋的信号传递。 还提供了用于表征NaV1.7特异性拮抗剂的体内和体外方法以及对NaV1.7介导的疾病的相应治疗潜力的评估。
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