Expression of alternatively spliced sodium channel α-subunit genes. Unique splicing patterns are observed in dorsal root ganglia

Christopher K. Raymond, John Castle, Philip Garrett-Engele, Christopher D. Armour, Zhengyan Kan, Nicholas Tsinoremas, Jason M. Johnson

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

Molecular medicine requires the precise definition of drug targets, and tools are now in place to provide genome-wide information on the expression and alternative splicing patterns of any known gene. DNA microarrays were used to monitor transcript levels of the nine well-characterized α-subunit sodium channel genes across a broad range of tissues from cynomolgus monkey, a non-human primate model. Alternative splicing of human transcripts for a subset of the genes that are expressed in dorsal root ganglia, SCN8A (Na v1.6), SCN9A (Nav1.7), and SCN11A (Nava.9) was characterized in detail. Genomic sequence analysis among gene family paralogs and between cross-species orthologs suggested specific alternative splicing events within transcripts of these genes, all of which were experimentally confirmed in human tissues. Quantitative PCR revealed that certain alternative splice events are uniquely expressed in dorsal root ganglia. In addition to characterization of human transcripts, alternatively spliced sodium channel transcripts were monitored in a rat model for neuropathic pain. Consistent down-regulation of all transcripts was observed, as well as significant changes in the splicing patterns of SCN8A and SCN9A.

Original languageEnglish (US)
Pages (from-to)46234-46241
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number44
DOIs
StatePublished - Oct 29 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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