Gene expression in animals with different acute responses to ethanol.
The genetic and environmental contributions to differences in response to ethanol have been examined widely using inbred strains, selected lines and genetically engineered (transgenic and 'knock-out') animals. In addition, recombinant inbred strains have been used to identify QTLs (chromosomal regions) associated with particular responses to ethanol. If the polymorphism that underlies such a QTL is localized within the regulatory region of a gene, it could alter the level or stability of the gene product (transcript). This possibility can be addressed by measuring mRNA levels in brains (or other tissue) of inbred or selected lines of animals using DNA microarray technology. In this paper, we review microarray studies conducted in animals that differ in their responses to ethanol. The results of these studies point out the critical nature of the experimental design, statistical analyses and 'filtering' procedures for producing interpretable data and identifying candidate genes. In particular, the determination of differentially expressed genes between selected lines of animals, and the localization of the differentially expressed genes within QTLs for the selected phenotype, dramatically increases the probability of identifying genes that contribute to that phenotype through differential expression. Microarray analysis can also be used to assess changes in gene expression that accompany transgene introduction and/or gene 'knock-out', which may modulate the influence of the targeted gene on behaviour.
Hoffman
Paula
P
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80045, USA. paula.hoffman@uchsc.edu
Tabakoff
Boris
B
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage* / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D010766:Phosphorylation; D040641:Quantitative Trait Loci / Q000187:drug effects* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol