Abstract

We have identified a total of seven genes or quantitative trait loci (QTLs) that determine loss of righting reflex (LORR) induced by ethanol. These loci have been named Lore I through 7 (Loss Of Righting: Ethanol). Together these genes explain more than 50% of the difference in ethanol-induced LORR between the LS and SS selected lines of mice. These QTLs are now identified only as relatively large genetic regions that are partially responsible for LORR differences. In our renewal we propose to pursue the next logical step: identification of the genes responsible for ethanol-induced LORR by molecular cloning of these genes. The major hurdles to be overcome in achieving this goal are: (1) localization of each Lore gene to as small a genetic region as possible: (Specific Aims A and B); (2) identifying and testing candidate genes within this area (Specific Aim C); (3) confirmation testing of proven candidate genes for involvement in the specification of LORR (future grants). After completion of Specific Aim A we will have defined a genetic region that could be as small as several cM; this will be narrowed down to a cM or less and moved to the molecular level (on the order of a few Mb of DNA)in Specific Aim B.
Specific Aim C will identify and test candidate genes for subsequent transgenic tests.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA008940-08
Application #
2894029
Study Section
Special Emphasis Panel (ZRG4-ALTX-3)
Project Start
1992-08-01
Project End
2001-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Colorado at Boulder
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309

  Publications

Noben-Trauth, Konrad; Latoche, Joseph R; Neely, Harold R et al. (2010) Phenotype and genetics of progressive sensorineural hearing loss (Snhl1) in the LXS set of recombinant inbred strains of mice. PLoS One 5:e11459
Parker, Clarissa Carlin; Ponicsan, Heather; Spencer, Robert Leon et al. (2008) Restraint stress and exogenous corticosterone differentially alter sensitivity to the sedative-hypnotic effects of ethanol in inbred long-sleep and inbred short-sleep mice. Alcohol 42:477-85
Bennett, B; Carosone-Link, P; Beeson, M et al. (2008) Genetic dissection of quantitative trait locus for ethanol sensitivity in long- and short-sleep mice. Genes Brain Behav 7:659-68
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
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
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
Proctor, William R; Wu, Peter H; Bennett, Beth et al. (2004) Differential effects of ethanol on gamma-aminobutyric acid-A receptor-mediated synaptic currents in congenic strains of inbred long and short-sleep mice. Alcohol Clin Exp Res 28:1277-83

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