Mouse Transcriptomic Fingerprints as Biomarkers for Chronic Alcohol Abuse

DESCRIPTION (provided by applicant): Alcohol abuse and its medical consequences have a significant negative impact on society, the economy and our health. Currently, however, no clinically available laboratory test can reliably diagnose excessive alcohol use throughout the population or predict the progression of alcohol-induced organ damage. NIAAA has therefore deemed it important to identify more sensitive and informative new biomarkers for chronic alcohol use and alcohol-induced organ damage to facilitate earlier diagnosis and detection of pathologies caused by problematic drinking. Genome Explorations Inc. (GenEx) proposes to use a mouse model system to identify gene expression profiles or "transcriptomic fingerprints" in blood cells that act as sensitive and specific indicators of chronic alcohol use and alcohol-induced liver damage. In Phase I of this SBIR application, GenEx will: 1) Develop and apply an experimental treatment for chronic ethanol abuse and alcoholic liver disease using inbred mouse strains commonly used in alcohol and toxicology research; 2) Generate transcriptome data sets for peripheral blood leukocytes from the treated mice using the Affymetrix platform and GeneChip Mouse 430 2.0 microarrays; and 3) Perform advanced data analysis to determine if gene expression profiles (transcriptomic fingerprints) can be identified as specific biomarkers for chronic ethanol exposure and/or the onset of ethanol-induced liver damage. In Phase II, GenEx will expand this analysis to other common inbred mouse strains and across a large genetic reference panel of BXD recombinant inbred mouse strains. Use of these additional strains will provide much greater analytical precision and help to refine potential fingerprints by reducing strain-specific effects. The use of BXD strains will also enable validation of the results by genetic correlational analysis using GenExQTL, a powerful new correlational database developed specifically for NIAAA. The development of transcriptomic biomarkers in these genetically defined mouse strains would provide a powerful tool for alcohol-related research and facilitate the development of new and more effective clinical biomarkers in people.