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Chunk #29 — IDENTIFICATION OF TRANSCRIPTION FACTORS CO-REGULATING THE EXPRESSION OF PREDISPOSING GENES

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Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain.
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Acute functional tolerance develops within a single exposure to ethanol and has been suggested to be a predisposing factor for the development of ethanol dependence [78]. A series of three studies by the same laboratory analyzed whole brain gene expression analysis in two replicate mouse lines selected for high or low acute functional tolerance to the loss of motor coordination produced by ethanol (HAFT/LAFT). The first study identified 144 differentially expressed transcripts [40]. Six of these genes lay within a bQTL for acute functional tolerance [79]. Binding sites for the transcription factor Cebpa were present in the promoter of five of the six candidate genes. The second study also combined gene expression and behavioral data from 26 BXD recombinant inbred strains, as described above for ethanol preference [39]. Twenty-two of the 275 genes differentially expressed in HAFT and LAFT mice were located both within an eQTL and a bQTL, and eight of these 22 candidate genes had expression levels correlated with acute functional tolerance to the incoordinating effects of ethanol in BXD strains. Further analysis of the candidate gene promoters