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GS1778 • Tabakoff et al 2003: Differential Gene Expression of acute functional tolerance to an incoordinating effect of ethanol (HAFT2 vs LAFT2)
Affymetrix oligonucleotide arrays to assess gene expression in brains of mice selectively bred for differences in acute functional tolerance to an incoordinating effect of ethanol (HAFT mice, high acute functional tolerance; LAFT mice, low acute functional tolerance)
HAFT2 vs LAFT2
Tabakoff B, Bhave SV, Hoffman PL
Selective breeding, quantitative trait locus analysis, and gene arrays identify candidate genes for complex drug-related behaviors.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Vol 23, pp. 4491-8
Acute functional tolerance to ethanol develops during a single exposure to ethanol; it has been suggested to be a predisposing factor for the development of ethanol dependence. Genetic determinants of acute functional tolerance, as well as of ethanol dependence, have been clearly demonstrated. We describe a novel approach that uses a combination of selective breeding (to segregate genes contributing to the phenotype of interest, i.e., acute functional tolerance to the incoordinating effect of ethanol), quantitative trait locus analysis (to define chromosomal regions associated with acute functional tolerance), and DNA microarray technology (to identify differentially expressed genes in the brains of the selected lines of mice) to identify candidate genes for the complex phenotype of ethanol tolerance. The results indicate the importance of a signal transduction cascade that involves the glutamate receptor delta2 protein, the Ephrin B3 ligand, and the NMDA receptor, as well as a transcriptional regulatory protein that may be induced by activation of the NMDA receptor (zinc finger protein 179) and a protein that can modulate downstream responses to NMDA receptor activation (peroxiredoxin), in mediating acute tolerance to the incoordinating effect of ethanol.
PUBMED: 12805289 Find other GeneSets from this publication