Transcriptional response to alcohol exposure in Drosophila melanogaster.

Abstract:

BACKGROUND:Alcoholism presents widespread social and human health problems. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Genetic factors that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance. RESULTS:We assessed whole-genome transcriptional responses following alcohol exposure and demonstrate immediate down-regulation of genes affecting olfaction, rapid upregulation of biotransformation enzymes and, concomitant with development of tolerance, altered transcription of transcriptional regulators, proteases and metabolic enzymes, including biotransformation enzymes and enzymes associated with fatty acid biosynthesis. Functional tests of P-element disrupted alleles corresponding to genes with altered transcription implicated 75% of these in the response to alcohol, two-thirds of which have human orthologues. CONCLUSION:Expression microarray analysis is an efficient method for identifying candidate genes affecting complex behavioral and physiological traits, including alcohol abuse. Drosophila provides a valuable genetic model for comparative genomic analysis, which can inform subsequent studies in human populations. Transcriptional analyses following alcohol exposure in Drosophila implicate biotransformation pathways, transcriptional regulators, proteolysis and enzymes that act as metabolic switches in the regulation of fatty acid metabolism as important targets for future studies of the physiological consequences of human alcohol abuse.

journal_name

Genome Biol

journal_title

Genome biology

authors

Morozova TV,Anholt RR,Mackay TF

doi

10.1186/gb-2006-7-10-r95

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

R95

issue

10

eissn

1474-7596

issn

1474-760X

pii

gb-2006-7-10-r95

journal_volume

7

pub_type

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