The objectives of this proposal are to identify genes whose expression is regulated by chronic exposure to ethanol using PCR differential display. Further identification and characterization of relevant differentially expressed genes will be done.Chronic exposure to ethanol produces physical dependence characterized by a withdrawal syndrome that includes life- threatening withdrawal convulsions. In addition there is sufficient evidence to suggest that genetics plays a significant role in the susceptibility to such convulsions. This research project attempts to determine which expressed genes may play a significant role in mediating susceptibility to ethanol-induced convulsions using an animal model. A genetically distinct line of mouse will be rendered physically dependent by chronic exposure to ethanol vapor. Upon removal of the mice from ethanol, brain mRNA will be extracted and subjected to PCR differential display. Genes which are differentially expressed as a result of chronic ethanol exposure will be further characterized by Northern blot analysis and selected genes will be cloned and sequenced. Information gathered from this type of research can lead to an understanding of the mechanisms by which ethanol exerts its effects as well as a greater understanding of the role of genetics in susceptibility to withdrawal convulsions.
| Rustay, N R; Boehm 2nd, S L; Schafer, G L et al. (2001) Sensitivity and tolerance to ethanol-induced incoordination and hypothermia in HAFT and LAFT mice. Pharmacol Biochem Behav 70:167-74 |
| Schafer, G L; Crabbe, J C; Wiren, K M (1998) Identification of neuroendocrine-specific protein as an ethanol-regulated gene with mRNA differential display. Mamm Genome 9:979-82 |
