Identification of neuroendocrine-specific protein as an ethanol-regulated gene with mRNA differential display

Chronic ethanol exposure produces changes in behavior that may result from effects of ethanol on gene expression. To identify potentially ethanol-regulated genes, mRNA differential display was used to screen the expressed genes in whole brain of mice chronically exposed to ethanol vapors. Mice genetically selected for susceptibility (Withdrawal Seizure-Prone; WSP) or resistance (Withdrawal Seizure-Resistant; WSR) to ethanol withdrawal convulsions were exposed to either ethanol vapor (ETOH group) or air (CTL group) for 72 h. A putative ethanol-regulated product was isolated; nucleotide sequence analysis of this product revealed >85% nucleotide identity to human neuroendocrine-specific protein (NSP) gene. Northern analysis of the expression of this product revealed hybridization to two transcripts (similar to 3.0 kb and 1.4 kb) on blots containing whole brain RNA, consistent with the transcript sizes of hNSP. Ethanol-induced regulation of mNSP was suggested in whole brain of WSP mice, but not in WSR mice, by Northern blot analysis. One transcript (3.0 kb) suggests a 26% increase in relative abundance in whole brain of ethanol-exposed WSP mice, while there was no effect of ethanol on abundance of the 1.4-kb transcript in WSP mice. No effects of ethanol were observed for WSR mice. These preliminary findings suggest that mNSP represents a novel ethanol-induced gene in mice selected for genetic susceptibility to severe ethanol withdrawal.