Cloning and characterization of a mouse sensory neuron tetrodotoxin- resistant voltage-gated sodium channel gene, Scn10a

Small-diameter sensory neurons associated with unmyelinated axons express a tetrodotoxin-insensitive (TTXi) voltage-gated sodium channel (VGSC) that may play an important role in the transmission of nociceptive information to the spinal cord. A TTXi VGSC, named SNS, that accounts for the tetrodotoxin-resistant sodium current described in sensory neurons has been cloned from rat dorsal root ganglia. Using recombinant λ phage clones encoding a mouse 129/SV genomic library, we have determined the detailed structure of the mouse SNS gene (Scn10a), including the location of exon- intron boundaries and the nucleotide sequence of the exons. The gene consists of 27 exons spanning approximately 90 kb on chromosome 9. Mouse SNS shows 95.3% overall amino acid identity to rat SNS and 98.5% identity throughout the putative transmembrane segments and the intracellular loop linking domains 3 and 4. The sizes of the exons and the exon-intron junction positions of the mouse SNS and the human skeletal muscle VGSC genes are remarkably conserved. These results provide the basis for an evolutionary comparison of sodium channels, the construction and analysis of a mouse SNS null mutant as a direct approach to understanding the biological function of SNS, and the identification of regulatory elements that are responsible for the tissue- and cell-specific expression of SNS.