The purpose of the Animal Core Component is to maintain and produce selectively bred lines and strains of mice for use by ARC investigators. Virtually all of these strain and lines of mice have been developed by the ARC as animal models for studying CNS mechanisms that mediate specific actions of ethanol and for identifying genes that mediate differences in ethanol sensitivity and acute tolerance. Maintenance and production of all mice are performed in the specific pathogen-free facilities of the Institute for Behavioral Genetics (IBG) located in Boulder, as needed, the animals are delivered from IBG to ARC investigators at UCHSC in Denver. Inbred strains of mice to be produced include the ILS, ISS, and the LS X SS Recombinant inbred strains that were derived from the LS and SS lines (selectively bred for differences in hypnotic sensitivity to ethanol). These strains and F2 generations derived from them are uniquely valuable for discovering genes that regulate hypnotic sensitivity to ethanol and for determining the behavioral, electrophysiological, and neurochemical effects attributable to polymorphisms in those genes. Another animal population that is invaluable for selective breeding experiments and for correlational studies of ethanol-related behaviors, the genetically heterogenous (HS) mice, will to be maintained and used by ARC investigators. Over the past 5 years, the ARC has developed, by selective breeding from the HS mice, a unique animal model for the study of acute functional tolerance (AFT). The Animal Core will continue to selectively breed for the high (HAFT) and low (LAFT) lines and will produce sufficient numbers of these mice, at each generation of selection, to meet the needs of the ARC investigators. In addition we propose to conduct several generations of selective breeding for lines of mice that differ in very rapid acute functional tolerance (VRAFT) to ethanol. Finally, as specific loci for genes that mediate differences in sensitivity and tolerance to ethanol are identified, the Animal Core will assist in selective breeding mice by genotype; thus, producing for ARC investigators congenic strains differing only at specified loci, e.g. at quantitative trait loci for ethanol sensitivity.
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