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 language | English |
|---|---|
| Pages (from-to) | 46234-46241 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 279 |
| Issue number | 44 |
| DOIs | |
| State | Published - Oct 29 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Expression of alternatively spliced sodium channel α-subunit genes. Unique splicing patterns are observed in dorsal root ganglia. / Raymond, Christopher K.; Castle, John; Garrett-Engele, Philip; Armour, Christopher D.; Kan, Zhengyan; Tsinoremas, Nicholas; Johnson, Jason M.
In: Journal of Biological Chemistry, Vol. 279, No. 44, 29.10.2004, p. 46234-46241.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of alternatively spliced sodium channel α-subunit genes. Unique splicing patterns are observed in dorsal root ganglia
AU - Raymond, Christopher K.
AU - Castle, John
AU - Garrett-Engele, Philip
AU - Armour, Christopher D.
AU - Kan, Zhengyan
AU - Tsinoremas, Nicholas
AU - Johnson, Jason M.
PY - 2004/10/29
Y1 - 2004/10/29
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M406387200
DO - 10.1074/jbc.M406387200
M3 - Article
VL - 279
SP - 46234
EP - 46241
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 44
ER -