D.K. Johnson, K.C. Goss, G.S. Sega, J.C. Schryver, M.J. Paulus, M.N. Ericson, and L.S. Webb 
Oak Ridge National Laboratory, P.O. Box 2009, Oak Ridge, TN 37831-8077 
1yy@ornl.gov 

The Life Sciences, Instrumentation and Controls, and Chemical and Analytical Sciences Divisions at Oak Ridge National Laboratory have launched a broad-based, high-throughput primary screening program designed to recover mouse mutations exhibiting subtle phenotypes. We are validating screening tools for behavioral, biochemical, morphological, and physiological changes induced by experimental mutagenesis by screening about 100 test-class mice per week. 

Our behavior-testing set currently includes the Porsolt forced swim test, rotorod, Poly-Track open-field activity system, and PhotobeaM activity monitor. We are introducing modifications into our cued and contextual fear conditioning test for learning and memory deficits and in our startle response tests, which have not proved adequate for reliable mutant identification so far. Biochemical tests include gas chromatography/mass spectrometry analysis of fatty acids, organic acids, and neurotransmitters in blood and tissue, as well as standard package analysis on an Abbott Cell-dyne 3500 Hematology Analyzer. For urine, we perform standard dipstick and specific gravity tests. 

Tool development includes a microCT scanner with image analysis software for mice, and a subdermal microbiosensor for the measurement of activity patterns, heart rate, body temperature, and, eventually, blood pressure. We are organizing joint screening programs with clinical and academic institutions across the state of Tennessee in order to broaden our screening and greatly enhance our expertise. Our goal is to maximize the number of whole-organism mutant phenotypes that we can detect in a high-throughput, broad-based, and cost-effective primary screening effort at ORNL. 

[Research sponsored jointly by the Office of Health and Environmental Research, USDOE, under contract DE-AC05-960R22464 with Lockheed Martin Energy Systems, Inc., and by the National Center for Human Genome Research (HG 00370).]