Mice expressing human voltage-gated sodium channels

Abstract

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 Nachannel gene, in particular a humanization of the one or more extracellular pore loops of a Na1.7 channel protein. Genetically modified non-human animals are also provided, wherein the genetic modification comprises replacement of an endogenous Nachannel gene, in particular a replacement of the endogenous Na1.7 gene with a human Na1.7 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 Na1.7 protein the surface of the excitable cells. Genetically modified mice are described, including mice that express the human or humanized Na1.7 gene from the endogenous Na1.7 locus, and wherein the mice comprise functional β-subunits.