Genetics and differential expression of NADH:ubiquinone oxidoreductase B8 subunit in brains of genetic strains of mice differing in voluntary alcohol consumption.
Inbred strains of mice remain a valuable resource for genetic dissection of complex traits including responses to drugs and chemicals, particularly alcohol. As a novel source of candidate genes for further analysis, we have used mRNA differential displays to identify genes with differential expression in the brains of ethanol-preferring (C57BL/6J) vs. ethanol-avoiding (A/J, BALB/c, and DBA/2J) strains, with and without ethanol i.p. treatments (4 g/kg). We report on one such gene, NADH:ubiquinone oxidoreductase B8 subunit, that has a higher expression in the C57BL/6J. Further, its expression also increases following ethanol treatment as compared to the three alcohol-avoiding strains. This regulatory feature follows three single nucleotide polymorphisms (SNPs) in the promoter region across the four strains studied. The four strains represent only two haplotypes, one C57BL/6J-specific and the other found in the three alcohol-avoiding strains. Interestingly, one of the observed SNPs (-687 A/G) is located in the putative TFIID binding site with potential to regulate the expression of this gene and contribute to genotype-specific alcohol responses and effects involving reactive oxygen species (ROS).
Harrison
Michelle
M
Molecular Genetics Unit, Department of Biology, University of Western Ontario, 307 Western Science Centre, London, Ontario, Canada.
Singh
Shiva M
SM
D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D042967:Electron Transport Complex I; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D035362:Transcription Factor TFIID / Q000378:metabolism
D012333:RNA, Messenger; D035362:Transcription Factor TFIID; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I