We propose to complete the construction of a large number of recombinant inbred strains (RIs) from the inbred Long Sleep (ILS) and the inbred Short Sleep (ISS) strains and to map genetically eight traits involved in alcohol action. This newly generate RI series will be useful in dozens of different behavioral analyses, while only one set of genotypic assessment swill need to be performed. From the single assessment of genotype will flow mapping results applicable to a myriad of various phenotypes that have been assessed in the parental strains (ILS and ISS) or in the LS and SS selected lines. The major disadvantages. associated with RI strains (lack of power in QTL identification and lack of resolution in mapping) are overcome through the use of such a large set of strains. The RI construction has already begun, funded by internal resources of the University of Colorado and the Institute for Behavioral Genetics and we propose to carry these RIs to the F22, which will allow greater than 98% fixation. At the completion of this project we will create an electronic data base allowing all alcohol researchers easy access to all of our results. We will also begin making arrangements to distribute these mice to searchers who wish to use them.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA011984-01A2
Application #
6045275
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Project Start
2000-03-01
Project End
2004-02-29
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
1
Fiscal Year
2000
Total Cost
$267,721
Indirect Cost
Name
University of Colorado at Boulder
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
Bennett, Beth; Downing, Chris; Carosone-Link, Phyllis et al. (2007) Quantitative trait locus mapping for acute functional tolerance to ethanol in the L x S recombinant inbred panel. Alcohol Clin Exp Res 31:200-8
Downing, Chris; Carosone-Link, Phyllis; Bennett, Beth et al. (2006) QTL mapping for low-dose ethanol activation in the LXS recombinant inbred strains. Alcohol Clin Exp Res 30:1111-20
Bennett, Beth; Downing, Chris; Parker, Clarissa et al. (2006) Mouse genetic models in alcohol research. Trends Genet 22:367-74
Bennett, Beth; Carosone-Link, Phyllis; Zahniser, Nancy R et al. (2006) Confirmation and fine mapping of ethanol sensitivity quantitative trait loci, and candidate gene testing in the LXS recombinant inbred mice. J Pharmacol Exp Ther 319:299-307
Bennett, B; Carosone-Link, P (2006) Replication of small effect quantitative trait loci for behavioral traits facilitated by estimation of effect size from independent cohorts. Genes Brain Behav 5:404-12
Sikela, James M; Maclaren, Erik J; Kim, Young et al. (2006) DNA microarray and proteomic strategies for understanding alcohol action. Alcohol Clin Exp Res 30:700-8
Haughey, Heather M; Kaiser, Alan L; Johnson, Thomas E et al. (2005) Norepinephrine transporter: a candidate gene for initial ethanol sensitivity in inbred long-sleep and short-sleep mice. Alcohol Clin Exp Res 29:1759-68
Bennett, Beth; Carosone-Link, Phyllis J; Lu, Lu et al. (2005) Genetics of body weight in the LXS recombinant inbred mouse strains. Mamm Genome 16:764-74
Rikke, Brad A; Yerg 3rd, John E; Battaglia, Matthew E et al. (2004) Quantitative trait Loci specifying the response of body temperature to dietary restriction. J Gerontol A Biol Sci Med Sci 59:118-25
Williams, Robert W; Bennett, Beth; Lu, Lu et al. (2004) Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis. Mamm Genome 15:637-47