The genomic determinants of alcohol preference in mice.
Searches for the identity of genes that influence the levels of alcohol consumption by humans and other animals have often been driven by presupposition of the importance of particular gene products in determining positively or negatively reinforcing effects of ethanol. We have taken an unbiased approach and performed a meta-analysis across three types of mouse populations to correlate brain gene expression with levels of alcohol intake. Our studies, using filtering procedures based on QTL analysis, produced a list of eight candidate genes with highly heritable expression, which could explain a significant amount of the variance in alcohol preference in mice. Using the Allen Brain Atlas for gene expression, we noted that the candidate genes' expression was localized to the olfactory and limbic areas as well as to the orbitofrontal cortex. Informatics techniques and pathway analysis illustrated the role of the candidate genes in neuronal migration, differentiation, and synaptic remodeling. The importance of olfactory cues, learning and memory formation (Pavlovian conditioning), and cortical executive function, for regulating alcohol intake by animals (including humans), is discussed.
Tabakoff
Boris
B
Department of Pharmacology, University of Colorado Denver School of Medicine, Mail Stop F-8303, P.O. Box 6511, Aurora, CO 80045-0511, USA. boris.tabakoff@ucdenver.edu
Saba
Laura
L
Kechris
Katherina
K
Hu
Wei
W
Bhave
Sanjiv V
SV
Finn
Deborah A
DA
Grahame
Nicholas J
NJ
Hoffman
Paula L
PL
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D005518:Food Preferences / Q000502:physiology*; D020869:Gene Expression Profiling; D008297:Male; D015201:Meta-Analysis as Topic; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci