Abstract
Establishing the mechanism of action of general anesthetics at the molecular level is difficult because of the multiple targets with which these drugs are associated. Inbred short sleep (ISS) and long sleep (ILS) mice are differentially sensitive in response to ethanol and other sedative hypnotics and contain a single quantitative trait locus (Lorp1) that accounts for the genetic variance of loss-ofrighting reflex in response to propofol (LORP). In this study, we used high-density oligonucleotide microarrays to identify global gene expression and candidate genes differentially expressed within the Lorp1 region that may give insight into the molecular mechanism underlying LORP. Microarray analysis was performed using Affymetrix MG-U74Av2 Genechips((R)) and a selection of differentiatly expressed genes was confirmed by semiquantitative reverse transcription-polymerase chain reaction. Global expression in the brains of ILS and ISS mice revealed 3423 genes that were significantly expressed, of which 139 (4%) were differentially expressed. Analysis of genes located within the Lorp1 region showed that 26 genes were significantly expressed and that just 2 genes (7%) were differentially expressed. These genes encoded for the proteins AWP1 (associated with protein kinase 1) and "BTB (POZ) domain containing 1," whose functions are largely uncharacterized. Genes differentially expressed outside Lorp1 included seven genes with previously characterized neuronal functions and thus stand out as additional candidate genes that may be involved in mediating the neurosensitivity differences between ISS and IL-S.
| Original language | English |
|---|---|
| Pages (from-to) | 697-704 |
| Number of pages | 7 |
| Journal | Anesthesia and Analgesia |
| Volume | 101 |
| DOIs | |
| Publication status | Published - 2005 |
Keywords
- RECOMBINANT INBRED STRAINS
- QUANTITATIVE TRAIT LOCI
- OLIGONUCLEOTIDE ARRAYS
- SEDATIVE-HYPNOTICS
- PROTEIN-KINASE
- PKN
- SENSITIVITY
- DOMAIN
- IDENTIFICATION
- PHOSPHORYLATES
Cite this
A microarray analysis of potential genes underlying the neurosensitivity of mice to propofol. / Lowes, Damon Anthony; Galley, Helen Frances; Lowe, Peter; Rikke, B. A.; Johnson, T. E.; Webster, Nigel Robert.
In: Anesthesia and Analgesia, Vol. 101, 2005, p. 697-704.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A microarray analysis of potential genes underlying the neurosensitivity of mice to propofol.
AU - Lowes, Damon Anthony
AU - Galley, Helen Frances
AU - Lowe, Peter
AU - Rikke, B. A.
AU - Johnson, T. E.
AU - Webster, Nigel Robert
PY - 2005
Y1 - 2005
N2 - Establishing the mechanism of action of general anesthetics at the molecular level is difficult because of the multiple targets with which these drugs are associated. Inbred short sleep (ISS) and long sleep (ILS) mice are differentially sensitive in response to ethanol and other sedative hypnotics and contain a single quantitative trait locus (Lorp1) that accounts for the genetic variance of loss-ofrighting reflex in response to propofol (LORP). In this study, we used high-density oligonucleotide microarrays to identify global gene expression and candidate genes differentially expressed within the Lorp1 region that may give insight into the molecular mechanism underlying LORP. Microarray analysis was performed using Affymetrix MG-U74Av2 Genechips((R)) and a selection of differentiatly expressed genes was confirmed by semiquantitative reverse transcription-polymerase chain reaction. Global expression in the brains of ILS and ISS mice revealed 3423 genes that were significantly expressed, of which 139 (4%) were differentially expressed. Analysis of genes located within the Lorp1 region showed that 26 genes were significantly expressed and that just 2 genes (7%) were differentially expressed. These genes encoded for the proteins AWP1 (associated with protein kinase 1) and "BTB (POZ) domain containing 1," whose functions are largely uncharacterized. Genes differentially expressed outside Lorp1 included seven genes with previously characterized neuronal functions and thus stand out as additional candidate genes that may be involved in mediating the neurosensitivity differences between ISS and IL-S.
AB - Establishing the mechanism of action of general anesthetics at the molecular level is difficult because of the multiple targets with which these drugs are associated. Inbred short sleep (ISS) and long sleep (ILS) mice are differentially sensitive in response to ethanol and other sedative hypnotics and contain a single quantitative trait locus (Lorp1) that accounts for the genetic variance of loss-ofrighting reflex in response to propofol (LORP). In this study, we used high-density oligonucleotide microarrays to identify global gene expression and candidate genes differentially expressed within the Lorp1 region that may give insight into the molecular mechanism underlying LORP. Microarray analysis was performed using Affymetrix MG-U74Av2 Genechips((R)) and a selection of differentiatly expressed genes was confirmed by semiquantitative reverse transcription-polymerase chain reaction. Global expression in the brains of ILS and ISS mice revealed 3423 genes that were significantly expressed, of which 139 (4%) were differentially expressed. Analysis of genes located within the Lorp1 region showed that 26 genes were significantly expressed and that just 2 genes (7%) were differentially expressed. These genes encoded for the proteins AWP1 (associated with protein kinase 1) and "BTB (POZ) domain containing 1," whose functions are largely uncharacterized. Genes differentially expressed outside Lorp1 included seven genes with previously characterized neuronal functions and thus stand out as additional candidate genes that may be involved in mediating the neurosensitivity differences between ISS and IL-S.
KW - RECOMBINANT INBRED STRAINS
KW - QUANTITATIVE TRAIT LOCI
KW - OLIGONUCLEOTIDE ARRAYS
KW - SEDATIVE-HYPNOTICS
KW - PROTEIN-KINASE
KW - PKN
KW - SENSITIVITY
KW - DOMAIN
KW - IDENTIFICATION
KW - PHOSPHORYLATES
U2 - 10.1213/01.ANE.0000160587.72827.B4
DO - 10.1213/01.ANE.0000160587.72827.B4
M3 - Article
VL - 101
SP - 697
EP - 704
JO - Anesthesia and Analgesia
JF - Anesthesia and Analgesia
SN - 0003-2999
ER -