My lab designs, produces, and tests novel mutant mice (knock-in and knock-out mice) that delineate genetic and environmental causes of excessive alcohol consumption. Knock-in mice contain a specific gene that is modified or mutated in order to study the effect of the gene on the animals' behavior. In knock-out mice, a specific gene is disabled in order to evaluate its function as a result of its absence. In addition to behavioral studies, I analyze brain samples from these mice using microarray techniques to evaluate ethanol's effect on brain gene expression. My results suggest that the deletion of any genes from this ethanol-sensitive gene "library" may in turn modify the motivation for drinking ethanol. My ultimate goal is to genetically increase the voluntary consumption of alcohol by combining (stacking) several different mutations.
Blednov, YA, Cravatt, BF, Boehm II, SI, Walker, D and Harris, RA. Role of endocannabinoids in alcohol consumption and intoxication: Studies of mice lacking fatty acid amide hydrolase. Neuropsychopharmacology, 32:1570-82, 2007.
Mulligan MK, Ponomarev I, Hitzemann RJ, Belknap JK, Tabakoff B, Harris RA, Crabbe JC, Blednov YA, Grahame NJ, Phillips TJ, Finn DA, Hoffman PL, Iyer VR, Koob GF, and Bergeson SE. Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis. PNAS, 103:6368-73 (2006).
Blednov YA, Bergeson SE, Walker D, Ferreira VM, Kuziel WA, and Harris RA. Perturbation of chemokine networks by gene deletion alters the reinforcing actions of ethanol. Behavioral Brain Res. 165:110-125 (2005).
Ponomarev I, Schafer GL, Blednov YA, Williams RW, Iyer VR, and Harris RA. Convergent analysis of cDNA and short oligomer microarrays, mouse null mutants, and bioinformatics resources to study complex traits. Genes, Brain & Behav., 3:360-8 (2004).
Blednov YA, Stoffel M, Alva H, and Harris RA. A pervasive mechanism for analgesia: activation of GIRK2 channels. Proc Natl Acad Sci U S A 100: 277-282 (2003).