A microarray analysis of potential genes underlying the neurosensitivity of mice to propofol.

Damon Anthony Lowes, Helen Frances Galley, Peter Lowe, B. A. Rikke, T. E. Johnson, Nigel Robert Webster

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)697-704
Number of pages7
JournalAnesthesia and Analgesia
Volume101
DOIs
Publication statusPublished - 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 journalArticle

Lowes, Damon Anthony ; Galley, Helen Frances ; Lowe, Peter ; Rikke, B. A. ; Johnson, T. E. ; Webster, Nigel Robert. / A microarray analysis of potential genes underlying the neurosensitivity of mice to propofol. In: Anesthesia and Analgesia. 2005 ; Vol. 101. pp. 697-704.
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