Localization of genes affecting alcohol drinking in mice.
The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.
Veterans Administration Medical Center, Oregon Health Sciences University, Portland.
T J
TJ
Phillips
J C
JC
Crabbe
P
P
Metten
J K
JK
Belknap
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D011995:Recombination, Genetic; D012640:Seizures / Q000235:genetics; D013045:Species Specificity; D013649:Taste / Q000235:genetics
D005819:Genetic Markers