Delineation of the role of nicotinic acetylcholine receptor genes in alcohol preference in mice.
The genetic factors that increase risk for alcohol and nicotine addiction have been elusive, although the frequent co-abuse of these drugs suggests they may act on a common biological pathway. A site of action for both nicotine and alcohol effects in the brain are neuronal nicotinic acetylcholine receptors (nAChR). This report explores the association between six nAChR subunit genes (Chrna3, Chrna4, Chrnb4, Chrnb2, Chrna5, and Chrna7) with alcohol preference (AP) using co-segregation of AP with nAChR subunit genotypes in a F(2) population produced from reciprocal crosses of alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) strains of mice. Polymorphisms located within the Chrna5-Chrna3-Chrnb4 cluster on mouse chromosome 9 were found to co-segregate with AP, with high-drinking F(2) mice carrying B6 alleles and low-drinking F(2) mice carrying D2 alleles. Further, the Chrnb4 and Chrna5 genes showed expression differences between B6 and D2 mice, which is compatible with their involvement in AP in mice and, potentially, alcohol abuse in humans.
Symons
Melissa N
MN
Molecular Genetics Unit, Department of Biology, University of Western Ontario, London, ON N6A 5B7, Canada.
Weng
Julia
J
Diehl
Eric
E
Heo
Eileen
E
Kleiber
Morgan L
ML
Singh
Shiva M
SM
D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000235:genetics; D003433:Crosses, Genetic; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000431:Ethanol; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; C486720:Chrnb4 protein, mouse; C523972:CHRNA5 protein, mouse