NEUROPEPTIDE RELEASE ASSAY FOR SODIUM CHANNELS

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 Na v 1.7 channel protein or a complete humanization of an endogenous Na v 1.7 gene, in particular a method of measuring nonciceptive function of dorsal root ganglia (DRG). Methods for using isolated DRG cultures from genetically modified non-human animals are also provided, wherein the isolated DRG express a human or chimeric Na v 1.7 protein on the surface, in particular measuring primary nociceptor 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 Na v 1.7 protein the cell surface. In vivo and in vitro methods for characterizing Na V 1.7-specific antagonists and evaluation of corresponding therapeutic potential for Na V 1.7-mediated disease are also provided.